Confusion in the Study of Immune Reconstitution Inflammatory Syndrome.
As a consequence of late presentation for HIV care, a significant proportion of individuals develop immune reconstitution inflammatory syndrome (IRIS) soon after initiation of antiretroviral therapy. Incidence, predictors, and models of pathogenesis of IRIS vary in the literature. Here we discuss factors that may contribute to this lack of consensus. We propose that different pathogens drive different types of IRIS and suggest that these clinical conditions should be studied individually and not grouped under the general heading of "IRIS."


Protease inhibitors alpha1-antitrypsin and ilomastat are not ototoxic in the chinchilla.
Proteases of both the serine and the metalloprotease families have been shown to play a role in the pathogenesis of otitis media. Inhibitors of proteases from each of these families have been shown to beneficially impact disease progression in a number of related chronic inflammatory conditions. The purpose of this study was to assess the safety of protease inhibitors when instilled into the middle ear, with a view to their potential use in the treatment of human otitis media. Prospective, randomized, controlled trial in the chinchilla model. After completing baseline auditory testing and bilateral transpalatal obstruction of the Eustachian tube, chinchillas received weekly transbullar injections of protease inhibitor (alpha1-antitrypsin, ilomastat, or both), vehicle, or saline. After 1 month, hearing was tested and the animals were sacrificed. Temporal bone histopathologic examination was performed. All treatment groups demonstrated a statistically insignificant average loss in long-term hearing (0 dB) for all measures using clicks and tones (P >.15 for all conditions). All treatment groups were statistically insignificantly different from one another (P =.5625). Histopathologic examination revealed no significant inner ear changes. Protease inhibitors that are currently under study in animal models and humans for the treatment of inflammatory diseases that are related to imbalances between protease and protease inhibitor have no significant toxic effect on the inner ear of chinchillas. These findings support the safety of further clinical trials using these inhibitors to treat middle ear inflammation.


Donepezil delays photoreceptor apoptosis induced by N-methyl-N-nitrosourea in mice.
Retinitis pigmentosa (RP) is a group of inherited retinal degeneration diseases characterized by photoreceptor cell death that causes visual disturbances and eventual blindness. Intraperitoneal injection of N-methyl-N-nitrosourea (MNU) causes photoreceptor loss, and is used to create an animal model for investigating the mechanisms that cause retinal degeneration diseases. Donepezil is an acetylcholinesterase inhibitor that has a protective effect on retinal ganglion cells in vitro and in vivo, and it is understood that donepezil increases the expression of a heat shock protein 70 (Hsp70), which serves to protect neurons. Hsp70 functions as a chaperone molecule that protects cells from protein aggregation and assists in the refolding of denatured proteins. In the present study, the effects of donepezil on photoreceptor survival in mice was investigated. It was observed that donepezil upregulates the expression of Hsp70, to increase resistance to MNU-induced photoreceptor cell apoptosis by using its anti-apoptotic properties. In addition, the present study observed that Hsp70 promotes photoreceptor cell survival by upregulating the expression levels of B-cell lymphoma 2 (Bcl-2). In conclusion, the results of the present study indicate that donepezil has the potential to be used as a treatment for retinal degenerative diseases.


Evidence for phosphorylation and oligomeric assembly of presenilin 1.
Pathogenic mutations in presenilin 1 (PS1) are associated with approximately 50% of early-onset familial Alzheimer disease. PS1 is endoproteolytically cleaved to yield a 30-kDa N-terminal fragment (NTF) and an 18-kDa C-terminal fragment (CTF). Using COS7 cells transfected with human PS1, we have found that phorbol 12, 13-dibutyrate and forskolin increase the state of phosphorylation of serine residues of the human CTF. Phosphorylation of the human CTF resulted in a shift in electrophoretic mobility from a single major species of 18 kDa to a doublet of 20-23 kDa. This mobility shift was also observed with human PS1 that had been transfected into mouse neuroblastoma (N2a) cells. Treatment of the phosphorylated CTF doublet with phage lambda protein phosphatase eliminated the 20- to 23-kDa doublet while enhancing the 18-kDa species, consistent with the interpretation that the electrophoretic mobility shift was due to the addition of phosphate to the 18-kDa species. The NTF and CTF eluted from a gel filtration column at an estimated mass of over 100 kDa, suggesting that these fragments exist as an oligomerized species. Upon phosphorylation of the PS1 CTF, the apparent mass of the NTF- or CTF-containing oligomers was unchanged. Thus, the association of PS1 fragments may be maintained during cycles of phosphorylation/dephosphorylation of the PS1 CTF.


Distinct solvent- and temperature-dependent packing arrangements of anti-parallel β-sheet polyalanines studied with solid-state 13C NMR and MD simulation.
Polyalanine (polyA) sequences are well known as the simplest sequence that naturally forms anti-parallel β-sheets and constitute a key element in the structure of spider and wild silkworm silk fibers. We have carried out a systematic analysis of the packing of anti-parallel β-sheets for (Ala)n, n = 5, 6, 7 and 12, using primarily 13C solid-state NMR and MD simulation. HFIP and TFA are frequently used as the dope solvents for recombinant silks, and polyA was solidified from both HFIP and TFA solutions by drying. An analysis of Ala Cβ peaks in the 13C CP/MAS NMR spectra indicated that polyA from HFIP was mainly rectangular but polyA from TFA was mainly staggered. The transition from the rectangular to the staggered arrangement in (Ala)6 was observed for the first time from the change in the Ala Cβ peak through heat treatment at 200 °C for 4 h. The removal of the bound water was confirmed by thermal analysis. This transition could be reproduced by MD simulation of (Ala)6 molecules at 200 °C after removal of the bound water molecules. In this way, the origin of the stability of the different packing arrangements of polyA was clarified.


Affinity-based growth factor delivery using biodegradable, photocrosslinked heparin-alginate hydrogels.
Photocrosslinkable biomaterials are promising for tissue engineering applications due to their capacity to be injected and form hydrogels in situ in a minimally invasive manner. Our group recently reported on the development of photocrosslinked alginate hydrogels with controlled biodegradation rates, mechanical properties, and cell adhesive properties. In this study, we present an affinity-based growth factor delivery system by incorporating heparin into photocrosslinkable alginate hydrogels (HP-ALG), which allows for controlled, prolonged release of therapeutic proteins. Heparin modification had minimal effect on the biodegradation profiles, swelling ratios, and elastic moduli of the hydrogels in media. The release profiles of growth factors from this affinity-based platform were sustained for 3weeks with no initial burst release, and the released growth factors retained their biological activity. Implantation of bone morphogenetic protein-2 (BMP-2)-loaded photocrosslinked alginate hydrogels induced moderate bone formation around the implant periphery. Importantly, BMP-2-loaded photocrosslinked HP-ALG hydrogels induced significantly more osteogenesis than BMP-2-loaded photocrosslinked unmodified alginate hydrogels, with 1.9-fold greater peripheral bone formation and 1.3-fold greater calcium content in the BMP-2-loaded photocrosslinked HP-ALG hydrogels compared to the BMP-2-loaded photocrosslinked unmodified alginate hydrogels after 8weeks implantation. This sustained and controllable growth factor delivery system, with independently controllable physical and cell adhesive properties, may provide a powerful modality for a variety of therapeutic applications.


Cougar (Puma concolor) Injury in the United States.
Human encounters with the cougar (Puma concolor) are rare in the United States but may be fatal. We performed a retrospective analysis of cougar attacks in the United States. We asked Fish and Wildlife Department officials from the 16 states in which cougars are known to live to identify all verified cougar attacks recorded in state history. Variables describing the human victim, cougar, and conditions surrounding the attack were recorded. The Fisher exact test was used for comparison. Ten states reported 74 cougar attacks from 1924 to 2018. Persons less than 18 y of age were heavily represented among victims; 48% were <18 y old, and 35% were less than 10 y old. Attacks were more common in the summer and fall months. Most attacks occurred during daylight hours. The head, neck, and chest were the most common anatomic sites of injury. Sixteen (46%) victims were hospitalized after being attacked, among the 35 victims with these data available. Eleven (15%) attacks were fatal among 71 reports with this information. None of the hospitalized victims died (P=0.02). No victim variables were predictive of death. Cougar attacks are uncommon but can be fatal. Attacks commonly affect children and young adults, although all age groups are at risk of attack and death. Most attacks occur during the daytime in the summer and fall. As development and recreational activities put humans in closer contact with cougars, establishing validated public health messaging is critical to minimize injurious encounters.


Comprehensive histologic analysis of ALK-rearranged lung carcinomas.
A subset (1% to 5%) of non-small-cell lung carcinomas harbors the EML4-ALK fusion gene. Data from previous studies on the histomorphology of ALK-rearranged lung cancer are inconsistent, and the specific histologic parameters that characterize this subset and how accurately such parameters predict underlying ALK abnormality remain uncertain. To answer these questions, we performed a comprehensive histologic analysis of 54 surgically resected, extensively sampled ALK-rearranged lung carcinomas and compared them with 100 consecutive resections of ALK-wild-type lung cancers. All 54 cases showed at least a focal adenocarcinoma component, and 3 and 2 cases had additional squamous and sarcomatoid differentiation, respectively. Solid or acinar growth pattern, cribriform structure, presence of mucous cells (signet-ring cells or goblet cells), abundant extracellular mucus, lack of lepidic growth, and lack of significant nuclear pleomorphism were more common in ALK-positive cancers. Two recognizable constellations of findings, a solid signet-ring cell pattern and a mucinous cribriform pattern, were present at least focally in the majority (78%) of ALK-positive tumors, but were rare (1%) in ALK-negative tumors. Multivariate analysis showed that a combination of these 2 patterns was the most powerful histologic indicator of ALK rearrangement. Characteristic histologies were present both in primary sites and in metastases. Thus, histologic findings may help to identify cases for ALK testing. However, none of the histologic parameters were completely sensitive or specific to ALK rearrangement, and histomorphology should not replace confirmatory molecular or immunohistochemical studies. ALK-positive cancers commonly showed coexpression of thyroid transcription factor-1 and p63, and its significance is currently unclear.


Longitudinal study of rotavirus infection and gastroenteritis in families served by a pediatric medical practice: clinical and epidemiologic observations.
During 29 months of prospective longitudinal study of diarrhea in the home, human rotaviruses (HRVs) infected one or more members in 51% of 65 families, 35 of 126 children (28%) and 16 of 124 adults (13%). Within the 33 affected families, 57% of 62 children and 25% of 65 adults were infected. HRV gastroenteritis peaked at 40/100 person years at ages 12 to 23 months and decreased to 5 episodes/100 person years in adults. Among 25 children 0 through 36 months of age who had HRV infection, 88% were symptomatic. Of the 22 children with symptomatic HRV infection, 1 required hospitalization and 8 were seen by their physician for supportive care. HRVs were found in 12% of 216 stools obtained during gastrointestinal illness, but in only 0.2% of 1238 non-illness stools tested. HRV infections were noted as early as October and as late as April. Of 33 families who were studied for 2 seasons, at least 1 individual in each of 3 families experienced HRV infections in both years, but only one, an adult, shed virus and had symptoms in both seasons.


Dexamethasone Implants in Diabetic Macular Edema Patients with High Visual Acuity.
To evaluate the effects of intravitreal dexamethasone (DEX) implants in patients affected by diabetic macular edema (DME) with high best-corrected visual acuity (BCVA) and contraindications to therapy with anti-vascular endothelial growth factor over a 12-month follow-up. In this interventional nonrandomized clinical study, 14 consecutive patients (14 eyes) affected by DME with a BCVA of 0.3 LogMAR or better were prospectively enrolled. All patients were treated with a sustained-release 700-μg DEX implant at baseline, revaluated every 6 weeks, and retreated on a pro re nata basis. Primary outcomes included changes in BCVA and central macular thickness (CMT). Secondary outcomes included number of implants, average period between injections, and incidence of side effects. At the 12-month examination, a significant improvement in mean BCVA was noted compared to baseline (from 0.25 ± 0.05 to 0.10 ± 0.07 LogMAR; p < 0.001); CMT decreased from 484 ± 127 to 311 ± 51 μm (p < 0.001). No differences in BCVA and CMT improvements were found between treatment- naïve patients and previously treated patients (p = 0.768 and 0.119, respectively). The mean number of implants was 1.71 ± 0.61 (range, 1-3). The mean period between the first and the second implant was 6.1 ± 1.6 months. The DEX implant on a pro re nata basis can be considered a beneficial approach for DME patients with high BCVA over a 12-month follow-up; functional and anatomical outcome of the patients significantly improved with few injections and a good safety profile.


The delineation of adriamycin extravasation using fluorescence microscopy.
Frozen-section fluorescence of Adriamycin extravasation in skin has been demonstrated to be an efficient method of detecting Adriamycin in tissue. Appropriate use of this technique as a guide to surgical treatment of infiltration is feasible, but it must await clinical trials.


Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition?
Individual patients show a large variation in their response to renin-angiotensin-aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as albuminuria and in hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer cardiovascular and, possibly, renal protection. To establish whether individual therapy resistance to RAASi can be overcome by adding an SGLT2 inhibitor, we assessed individual albuminuria responses in patients exposed to both RAASi and the SGLT2 inhibitor dapagliflozin. We used data from a randomized controlled cross-over trial designed to assess the albuminuria-lowering effect of 6-week treatment with dapagliflozin 10 mg/d. We extracted from the electronic medical records data on the albuminuria response upon initiation of RAASi before the trial period, and analysed individual albuminuria responses to RAASi and to dapagliflozin. We retrieved data on RAASi for 26 patients (age, 62 years [SD, 8]; female gender, 6 [23%]; 24-hour urinary albumin excretion, 521 [187-921] mg/24 h). The mean albuminuria-lowering response to RAASi was 26.5% (range, -76.1% to 135.1%). The addition of dapagliflozin res in a further reduction of 34.9%, (range, -83.9 to 94.2). Interestingly, the albuminuria response to RAASi significantly correlated with the response to dapagliflozin (Pearson correlation coefficient, 0.635 [95% CI, 0.328-0.821]; P < .001), indicating that patients who did not respond to RAASi also did not respond to dapagliflozin. We concluded that individual therapy resistance to RAASi cannot be overcome with the addition of a completely different class of drugs, SGLT2 inhibitors. These data suggest that the individual drug response is an intrinsic individual characteristic, possibly unrelated to the type of intervention, unless the mode of action of dapagliflozin on albuminuria is through the RAAS.


Co-purification of bone resorbing activity and adenylate cyclase stimulating activity from human tumours associated with the humoral hypercalcaemia of malignancy.
We have partially purified a tumour factor capable of stimulating both bone resorption in vitro and cAMP accumulation in osteoblastic ROS 17/2 cells from three human tumours associated with humoral hypercalcaemia of malignancy. Purification of tumour factor by sequential acid urea extraction, gel filtration and cation-exchange chromatography, reverse-phase high performance liquid chromatography followed by analytical isoelectric focussing provided a basic protein (pI greater than 9.3) with a molecular weight of approximately 13,000 as a major component of the final preparation which retained both the two bioactivities. Bone resorbing activity and cAMP-increasing activity in purified factor correlated with each other. cAMP-increasing activity of the factor was heat- and acid-stable, but sensitive to alkaline ambient pH. Treatment with trypsin destroyed cAMP-increasing activity of the factor. Synthetic parathyroid hormone (PTH) antagonist, human PTH-(3-34) completely inhibited the cAMP-increasing activity of the factor. The results suggest that this protein factor, having its effects on both osteoclastic and osteoblastic functions, may be involved in development of enhanced bone resorption in some patients with humoral hypercalcaemia of malignancy.


Evaluation of a new latex test and a new enzyme immunoassay for determination of rubella immunity.
A new enzyme immunoassay (Rubenostika; Organon Teknika, Turnhout, Belgium), a new latex agglutination test (Rubalex; Orion Diagnostica, Espoo, Finland), and three other accepted methods for the determination of rubella immunity were compared with a standard hemagglutination inhibition assay. Of 224 serum samples tested, 54 (24%) were nonreactive and 24 (11%) were low titered. All procedures were very specific (94 to 100%). Rubenostika was the least sensitive method (88%), and Rubalex was the most sensitive (98%).


New method of immobilization of microbial cells by capture on the surface of insoluble pyridinium-type resin.
A new method for the immobilization of microbial cells has been developed. Whole cells of Escherichia coli with aspartase activity were immobilized by capture on the surface of cross-linked poly(N-benzyl-4-vinylpyridinium bromide) containing styrene (BVPS resin), an insoluble pyridinium-type resin. When a suspension of the bacterial cells in buffer solution was passed through a glass column containing beads of BVPS resin, the cells were captured on the resin surface and formed an immobilized cell system. A fixed-bed column reactor containing 300 mg of the bacterial cells immobilized by capture on 10 g of BVPS resin beads was used for the preparation of L-aspartic acid from ammonium fumarate. Continuous operation of tne bioreactor produced L-aspartic acid in a quantitative yield when the influent substrate concentration was 0.1M and the flow rate was 0.41-0.83 bed volumes per hour at pH 7.4-7.7 at 30 degrees C.


An in-depth appraisal of clinico-biochemical and radiological findings of COVID-19 patients during the COVID-19 pandemic in a dedicated COVID Care Hospital in Eastern India and its outcome in relation to the COVAXIN vaccination status: A 2-year study.
COVID-19 pandemic hit Odisha province from April 2020 to December 2020, then from April 2021 to August 2021 and from February 2022 to April 2022 as the first, second, and third waves, respectively, with the most severe form witnessed during the second wave. Kalinga Institute of Medical Sciences hospital in Odisha was declared a Dedicated COVID Hospital (DCH) during those three waves and witnessed 9485 cases of admissions among which there were 1214 deaths. COVAXIN vaccination of the vulnerable population was launched in February 2021 onwards. This study has been done to know the clinic-biochemical profiles, radiologic findings of COVID-19 admitted patients, the predictors of mortality in the second wave, and clinical outcomes in the three waves in relation to COVAXIN vaccination status. This was a serial three-round retrospective study from the electronic medical records using multistage random sampling where we collected and critically analyzed the demographic, and all the relevant possible health data of the cases that consist of 514 cases admitted in three waves. The data from death certificates among the 555 cases in the second wave have been analyzed to conclude predictors of mortality. Mortality increased with age, male gender, comorbidities, and raised C-reactive protein level. High NL ratio, extent of pulmonary involvement. There was a wide variation in incidence and spectrum of illness starting from 79% incidence of mild symptomatic in the initial and third wave, but remained in the range of 35-65% in the second wave, respectively, and the most noticeable symptomatic illness was that of the upper respiratory tract. In fulminant cases, the mode of presentations was severe pneumonia and acute respiratory distress syndrome. Males were more sufferers than females. Children had better outcomes compared to adults. COVID-associated coagulopathy had a normal platelet count. Subsequently, in 2021 year onwards vaccination of the vulnerable population was launched in a phased manner that changed the dynamics of the disease outcome by better survival chances despite intercurrent COVID infection by induction of herd immunity. On the contrary, there was a higher prevalence of serious illness among non-vaccinated individuals. While the cases continued during the second wave of the pandemic, long COVID became a clinical entity of symptomatic that persisted or recurred among the COVID illness recovered cases after reverse transcriptase polymerase chain reaction results for COVID-19 became negative. The symptoms consisted of fatigue, cough, dyspnea as pulmonary manifestations and extra-pulmonary involvement of the cardiac, renal, and central nervous systems and the pulmonary imaging features consisted of interstitial pneumonia, consolidation, cavity pattern, and prone to microbial infection. These events lead to morbidity and admission. Coinciding with the vaccination of all population of Odisha province with the first dose of the vaccine by around the period of the first quarter of 2022, there was a new variant named Omicron responsible in the third wave, in which the majority of the admitted cases had.mild upper respiratory illness. This was not as lethal as its predecessors due to its lower propensity to invade the lungs and blood vessels. Immune dysregulation plays a central role in the pathogenesis of the manifestations. Vaccine-induced protection and the induction of herd immunity played a proactive role in the waning of the severity of clinical presentations.


The epidemiology of shigellosis in Israel.
Analysis of Shigella isolates referred for serotyping to the Central Shigella Reference Laboratory has revealed a slight predominance of S. sonnei (47%) over S. flexneri (44%) in Israel. In female patients, the predominance of S. sonnei isolates was more accentuated (54 v. 37.5% for S. flexneri). On the other hand, an increased incidence of S. flexneri was observed in military personnel (59 v. 32% for S. sonnei), and even more so in the Arab population (69 v. 19%). Incidence peaked in summer (July, August) for all subgroups.


Expression and light-dependent translocation of β-arrestin in the visual system of the terrestrial slug Limax valentianus.
Vertebrates, cephalopods and arthropods are equipped with eyes that have the highest spatiotemporal resolution among the animal phyla. In parallel, only animals in these three phyla have visual arrestin specialized for the termination of visual signaling triggered by opsin, in addition to ubiquitously expressed β-arrestin that serves in terminating general G protein-coupled receptor signaling. Indeed, visual arrestin in Drosophila and rodents translocates to the opsin-rich subcellular region in response to light to reduce the overall sensitivity of photoreceptors in an illuminated environment (i.e. light adaptation). We thus hypothesized that, during evolution, visual arrestin has taken over the role of β-arrestin in those animals with eyes of high spatiotemporal resolution. If this is true, it is expected that β-arrestin plays a role similar to visual arrestin in those animals with low-resolution eyes. In the present study, we focused on the terrestrial mollusk Limax valentianus, a species related to cephalopods but that has only β-arrestin, and generated antibodies against β-arrestin. We found that β-arrestin is highly expressed in photosensory neurons, and translocates into the microvilli of the rhabdomere within 30 min in response to short wavelength light (400 nm), to which the Limax eye exhibits a robust response. These observations suggest that β-arrestin functions in the visual system of those animals that do not have visual arrestin. We also exploited anti-β-arrestin antibody to visualize the optic nerve projecting to the brain, and demonstrated its usefulness for tracing a visual ascending pathway.


Concentrations of anti-Müllerian hormone in the domestic cat. Relation with spay or neuter status and serum estradiol.
Female cats with unknown history can be diagnosed as spayed or intact with a GnRH-stimulation test or an LH test independent of the stage in the estrous cycle. However, although most females are correctly diagnosed with the LH test, the sensitivity and specificity are not 100%. The GnRH-stimulation test, although reliable, requires an injection of buserelin 2 hours before the blood sample is collected. Granulosa cells are the only cell type that produces anti-Müllerian hormone (AMH) in females, whereas Sertoli cells produce AMH in males. Anti-Müllerian hormone has been linked to spay status in dogs and cats and to ovarian and testicular pathology and fertility in different species. Our aim was to evaluate serum AMH concentrations in spayed female cats and in intact female cats of known age and reproductive stage (inactive ovaries or luteal phase). In addition, our aim was to compare serum AMH concentrations in intact and neutered male cats. We analyzed serum AMH concentrations in 15 spayed and 16 intact females and in 15 intact and 12 neutered male cats. Serum AMH was below the lowest standard point (<0.14 ng/mL) in all spayed females and neutered males, ranged between 1.3 and 19.0 ng/mL in the intact females and between 4.8 and 81.3 ng/mL in intact males. Thus, the AMH test had 100% sensitivity and specificity to diagnose the presence or absence of ovaries and testes in this study. In addition, in contrast to serum estradiol, serum AMH was not affected by buserelin stimulation (P = 0.459). Serum AMH was not correlated with serum estradiol before (rs = -0.188, P = 0.519) or after (rs = 0.335, P = 0.242) buserelin stimulation in the intact females. Four 6-month-old intact cats (two females and two males) had the highest AMH concentrations which in the females might represent a prepubertal peak previously described in other species and in males is likely due to high concentrations before puberty. In conclusion, we found that the AMH Gen II ELISA is reliable for diagnosing spay and neuter status of cats and that the domestic cat might be an interesting model for studies on AMH dynamics.


Ligand oxidations in high-spin nickel thiolate complexes and zinc analogues.
Oxidations of a trigonal-bipyramidal, high-spin Ni(II) dithiolate complex of a pentadentate, N3S2-donor ligand, N1,N9-bis(imino-2-mercaptopropane)-1,5,9-triazanonane) nickel(II), and the structurally analogous Zn(II) complex, lead to oxidations of the ligand. Oxidation of the Ni(II) complex with I2 produces a novel Ni(II) macrocyclic cationic complex containing a monodentate disulfide ligand (2). Crystals of the I3- salt of the complex form in the triclinic space group P(1) with cell dimensions a=8.508(3) A, b=9.681(2) A, c=14.066(4) A, angles alpha=90.97(2) degrees , beta=91.61(3) degrees , gamma=90.83(2) degrees , and Z=2. The structure was refined to R=6.31% and Rw=16.63% (I > 2sigma(I)). Oxidation of the Ni(II) complex with O2 leads to the formation of a novel pentadentate bis-iminothiocarboxylate complex with trigonal-bipyramidal geometry (3). This neutral product crystallizes in the monoclinic space group P21/c with cell dimensions a=13.625(3) A, b=7.605(5) A, c=14.902(4) A, angles alpha=gamma=90 degrees, beta=102.81(2) degrees , and Z=4. The structure was refined to R=7.18% and Rw=17.86% (I > 2sigma(I)). Oxidation of the Zn(II) dithiolate analogue with O2 leads to the formation of the Zn(II) complex of the pentadentate bis-iminothiocarboxylate ligand. The neutral complex is isomorphous with the Ni(II) complex and crystallizes in the monoclinic space group P2(1)/c with cell dimensions a=13.8465(4) A, b=7.6453(2) A, c=15.0165(6) A, angles alpha=gamma=90 degrees , beta=103.2140(11) degrees , and Z=4. The structure was refined to R=3.96% and Rw=9.45% (I > 2sigma(I)). Details of the crystal structures are reported. Kinetics of the O2 reactions show that the reactions of the Ni(II) and Zn(II) dithiolates follow the rate law, Rate=k2[1][O2], with k2=1.81 M(-1) s(-1) for the Ni(II) complex and k2=1.93 x 10(-2) M(-1) s(-1) for the Zn(II) complex. The O2 oxidation of the high-spin Ni(II) thiolate complex was found to follow a similar oxidation mechanism to those of low-spin Ni(II) complexes, which form transient persulfoxide intermediates that yield S-oxidation products. In the case of the high-spin system reported here, the transient persulfoxide intermediate gives rise to an alternative ligand oxidation product, a bis-iminothiocarboxylate complex, because of the reactivity of the ligand, which contains a methylene with acidic H atoms alpha to the thiolate sulfur. The proposed mechanism is supported by studies of the analogous Zn dithiolate complex, which gives rise to the analogous bis-iminothiocarboxylate product (5).


MicroRNA‑139 suppressed tumor cell proliferation, migration and invasion by directly targeting HDGF in epithelial ovarian cancer.
The current study investigated the expression and functional roles of microRNA‑139 (miR‑139) on human epithelial ovarian cancer (EOC). Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to measure miR‑139 expression in EOC tissues and cell lines. The effects of miR‑139 on EOC cell proliferation, migration and invasion were assessed using MTT, cell migration and invasion assays, respectively. Subsequently, the molecular mechanism underlying the tumor suppressive roles of miR‑139 on EOC was determined by bioinformatics analysis, RT‑qPCR, western blotting and the luciferase reporter assay. According to the results, it was identified that miR‑139 was significantly downregulated in EOC tissues and cell lines. In addition, restoration of miR‑139 suppressed tumor cell proliferation, migration and invasion in EOC. Furthermore, hepatoma‑derived growth factor (HDGF) was identified as a target of miR‑139 in EOC. Upregulation of HDGF could rescue the inhibitory effects exerted by miR‑139 overexpression on EOC cell proliferation, migration and invasion. Collectively, the results indicated that miR‑139 was downregulated in EOC, and acted as a tumor suppressor by directly targeting HDGF. To the best of our knowledge, this was the first study to identify that miR‑139 contributes to the growth and metastasis of EOC.


Association of Hyperglycemia with In-Hospital Mortality and Morbidity in Libyan Patients with Diabetes and Acute Coronary Syndromes.
Hyperglycemia on admission and during hospital stay is a well-established predictor of short-term and long-term mortality in patients with acute myocardial infarction. Our study investigated the impact of blood glucose levels on admission and in-hospital hyperglycemia on the morbidity and mortality of Libyan patients admitted with acute coronary syndromes (acute myocardial infarction and unstable angina). In this retrospective study, the records of patients admitted with acute coronary syndrome to The 7th Of October Hospital, Benghazi, Libya, between January 2011 and December 2011 were reviewed. The level of blood glucose on admission, and the average blood glucose during the hospital stay were recorded to determine their effects on in-hospital complications (e.g. cardiogenic shock, acute heart failure, arrhythmias, and/or heart block) and mortality. During the study period, 121 patients with diabetes were admitted with acute coronary syndrome. The mortality rate in patients with diabetes and acute coronary syndrome was 12.4%. Patients with a mean glucose level greater than 200mg/dL had a higher in-hospital mortality and a higher rate of complications than those with a mean glucose level ≤200mg/dL (27.5% vs. 2.6%, p<0.001 and 19.7% vs. 45.5%, p=0.004, respectively). There was no difference in in-hospital mortality between patients with a glucose level at admission ≤140mg/dL and those admitted with a glucose level >140mg/dL (6.9% vs. 14.3%; p=0.295), but the rate of complications was higher in the latter group (13.8% vs. 34.1%; p=0.036). Patients with admission glucose levels >140mg/dL also had a higher rate of complications at presentation (26.4% vs. 6.9%; p=0.027). In patients with diabetes and acute coronary syndrome, hyperglycemia during hospitalization predicted a worse outcome in terms of the rates of in-hospital complications and in-hospital mortality. Hyperglycemia at the time of admission was also associated with higher rate of complications particularly at the time of presentation.


Mitral valve bio-prosthesis and annuloplasty thrombosis during extracorporeal membrane oxygenation: case series.
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a well-recognized form of haemodynamic support for patients with refractory cardiogenic shock, who are unable to be weaned off cardiopulmonary bypass. Thrombosis or bleeding from cannula sites or surgical wounds are the leading cause of morbidity and mortality in these patients, and presents a delicate balance of anticoagulation during management of patients undergoing circulatory support. In this case series, we discuss three cases of patients undergoing mitral valve replacements or repair with thrombosis of their new bio-prosthesis in the immediate post-operative setting. All three patients were supported with VA-ECMO post-operatively, and thrombosis occurred despite anticoagulation. During extracorporeal membrane oxygenation, the reduced flow throughout the heart increases the risk of intra-cardiac thrombosis. This is of particular importance in the context of mitral valve replacements and repairs, where the bio-prosthesis is an additional risk factor for thrombosis. Our cases demonstrate the morbidity and mortality of such complications, with the likely aetiology being low transvalvular flow in a newly inserted valve combined with the pro-thrombotic state created by the VA-ECMO circuit.


Studies on effect of temperature and time on textural and rheological properties of starch isolated from traditional rice cultivars of Kashmir (India).
In the present study, the effect of storage temperature and time on the textural and rheological properties of starch gels from seven different rice cultivars having higher amylose content than the hybrid rice varieties were evaluated. Water solubility and swelling power increased with every 10C increase in temperature due to granule swelling and solubilization of starch wherein the maximum solubility was found in starch of Koshkari rice cultivar (0.721 to 13.50) and swelling power in starch of Zag rice cultivar (3.688 to 10.806). However, syneresis in the analyzed rice starch gels had shown a fluctuating trend for each individual cultivar at different storage periods in which the cultivars Zag had shown the highest values of syneresis during storage (4.123 to 4.957%). In the texture profile analysis of starch gel of these cultivars, Mushki Budgi had the highest value of hardness (0.723N), gumminess (36.262) and chewiness (31.056). The turbidity values of gelatinized starch suspensions from different rice cultivars increased progressively during the first 4 days of storage followed by a decrease in the 5th day coupled with slight increase in the 6th day. The highest turbidity was found in Zag ranging from 1.47 to 1.67 during refrigerated storage after 6 days. The rheological analysis revealed that Zag indicated the highest value of TG' (76.96C) whereas cultivars Koshkari and Mushki Kandi had shown the lowest value of TG' (74.34C) upon heating cycle. Rheological properties of starch are affected by amylose contents, lipid contents, branch chain length distribution of amylopectin. The starch from different varieties depicted variable textural and rheological properties at various time: temperature combinations. No research has been reported to explore the effect of time and temperature on the textural and rheological properties of starch isolated from these traditional rice cultivars. The starches from traditional rice cultivars (native or indigenous rice cultivars of a region) indicated novel characteristic as compared to other cultivars in terms of their higher amylose content, starch yield, purity, clarity, solubility, syneresis, turbidity, and rheology. The novelty of this research was to exploit the desirable properties of starch obtained from traditional rice cultivars that had better characteristics than the hybrid varieties. This in turn led the various agencies to motivate the farmers to encourage their cultivation, provide an essential platform to scientists to inherit their valuable characteristics.


DNA electron microscopy.
In recent years DNA electron microscopy has become a tool of increasing interest in the fields of molecular genetics and molecular and cell biology. Together with the development of in vitro recombination and DNA cloning, new electron microscope techniques have been developed with the aim of studying the structural and functional organization of genetic material. The most important methods are based on nucleic acid hybridizations: DNA-DNA hybridization (heteroduplex, D-loop), RNA-DNA hybridization (R-loop), or combinations of both (R-hybrid). They allow both qualitative and quantitative analysis of gene organization, position and extension of homology regions, and characterization of transcription. The reproducibility and resolution of these methods make it possible to map a specific DNA region within 50 to 100 nucleotides. Therefore they have become a prerequisite for determining regions of interest for subsequent nucleotide sequencing. Special methods have been developed also for the analysis of protein-DNA interaction: e.g., direct visualization of specific protein-DNA complexes (enzymes, regulatory proteins), and analysis of structures with higher complexity (chromatin, transcription complexes).


Evolution of the genomic recombination rate in murid rodents.
Although very closely related species can differ in their fine-scale patterns of recombination hotspots, variation in the average genomic recombination rate among recently diverged taxa has rarely been surveyed. We measured recombination rates in eight species that collectively represent several temporal scales of divergence within a single rodent family, Muridae. We used a cytological approach that enables in situ visualization of crossovers at meiosis to quantify recombination rates in multiple males from each rodent group. We uncovered large differences in genomic recombination rate between rodent species, which were independent of karyotypic variation. The divergence in genomic recombination rate that we document is not proportional to DNA sequence divergence, suggesting that recombination has evolved at variable rates along the murid phylogeny. Additionally, we document significant variation in genomic recombination rate both within and between subspecies of house mice. Recombination rates estimated in F(1) hybrids reveal evidence for sex-linked loci contributing to the evolution of recombination in house mice. Our results provide one of the first detailed portraits of genomic-scale recombination rate variation within a single mammalian family and demonstrate that the low recombination rates in laboratory mice and rats reflect a more general reduction in recombination rate across murid rodents.


Assessment of genetic diversity and relationships among maize (Zea mays L.) Italian landraces by morphological traits and AFLP profiling.
In the present study we have analyzed the genetic diversity pattern in a sample of 54 Italian maize landraces, using morphological traits and molecular markers. Although the 54 landraces surveyed in this study were restricted to Lombardy, the core region of maize production in Italy, our data revealed a large genetic heterogeneity for both morphological and molecular traits in the accessions analyzed. Additionally, our data confirm that the AFLP markers produced a high frequency of polymorphic bands and were able to unequivocally fingerprint each of the landraces considered. Cluster analysis based on AFLP markers displayed a clearer separation of the accessions in comparison to morphological data. Different populations were divided into four major clusters reflecting the geographical origin and seasonal employment of the landraces analyzed. Molecular analysis of variance showed significant (P < 0.01) differences among groups, among populations within groups, and among individuals within populations. Approximately 74% of the total variance could be attributed to differences within populations. Conversely, a lower level of differentiation was detected among groups (approximately 4%). Regarding population structures, the genetic distance between populations (FST = 0.25 +/- 0.3) and the degree of inbreeding within groups (FSC = 0.22 +/- 0.2), did not diverge significantly, while both significantly differed from the degree of relatedness between markers within groups (FCT = 0.04 +/- 0.03). Results are discussed in relation to a suitable conservation method.


Disaster Preparedness in Primary Care: Ready or Not?
PurposeTo assess perceptions and attitudes toward disasters and disaster planning among outpatient primary care leaders. Written surveys and semi-structured interviews of non-physician clinical managers and physician medical directors were conducted using the 2009 H1N1 pandemic as a case-based scenario at 5 university-affiliated family medicine clinics. Domains assessed included perceived pandemic threat; value, existence, and barriers to creating personal disaster plans; staff absenteeism estimates; barriers to work attendance. Quantitative and qualitative data were analyzed using descriptive statistics and content analysis with identification and coding of common themes, respectively. All 12 invited leaders participated and believed a personal disaster plan was important but only 2 had plans. None had ever discussed with their staff the importance of having a personal disaster plan. Two common barriers in creating a plan were low threat perception level and never considering the possibility of pandemic influenza. Only half of respondents could list common barriers preventing staff from working. Staff were confident employees would come to work during a disaster. Outpatient primary care leaders may hold misconceptions regarding future disasters, underestimate their potential impact on clinics, and lack personal preparedness. Further investigation and interventions are needed to ensure clinics can be prepared so they can function and help hospital and emergency services when disasters strike. (Disaster Med Public Health Preparedness. 2018;12:644-648).


Effect of dextranase on plaque formation and caries development in the rat.
Plaque formation and caries development were studied in 0-M rats fed Diet 2000 and infected with S. mutans 6715 and fecal flora from older caries-active rats. Merck dextranase, Beckman dextranase or Beckman glucanase 447 were administered singly or in combination to groups of 12 rats either as an addition to the diet or as a "mouthwash" twice daily, 5 per week. All enzymes studied were associated with significant inhibition of both plaque formation and caries development, especially on the buccal and lingual surfaces.


Experimental otitis media in mice. Immunohistochemical observations.
In order to identify T cells and B cells in the middle ear (ME) mucosa, immunohistochemical observations were performed on mice which were induced with immune-mediated otitis media with effusion (OME). C3H/HeN mice were challenged with dinitrophenylated ovalbumin in the ME, 2 weeks after the systemic immunization. At 1, 3 and 7 days post challenge, the mice were sacrificed, and IgG-, IgA- or IgM-positive cells, as well as Lyt-1- or Lyt-2-positive cells, were observed in the subepithelial layer of ME. IgG- or IgA-positive lymphocytes were detected at 7 days post challenge, whereas IgM-positive cells were rarely seen. At 3 days post challenge, the number of Lyt-1-positive lymphocytes exceeded that of Lyt-2-positive lymphocytes; however, at 7 days post challenge they were similar. Previous studies have suggested that immune complexes are a key factor in the generation of immune-mediated OME. However, it seems possible that delayed type hypersensitivity may contribute to the pathogenic mechanism of OME.


Solution-processed organic photovoltaic cells with anthracene derivatives.
Solution-processed small-molecule bulk heterojunction photovoltaic cells are fabricated by using [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) as electron acceptor and triisopropylsilylethynyl anthracene (TIPSAnt) derivatives substituted with naphthalene (TIPSAntNa) and bithiophene (TIPSAntBT) as electron donors. In contrast to TIPS-pentacene, the TIPSAnt derivatives are not susceptible to Diels-Alder reactions with PCBM when processed in solution, as confirmed by UV/Vis measurements. Photoluminescence quenching measurements show exciton diffusion lengths of 5 and 3 nm for TIPSAntBT and TIPSAntNa, respectively. Blending TIPSAntBT and TIPSAntNa with PCBM (1:1, 1:2, 1:3, and 1:4 weight ratios) produces films that possess adequate hole and electron mobilities. The morphological changes that result from varying the blending ratio range from obvious phase-segregated crystalline domains at a 1:1 ratio to homogeneous, nearly amorphous phases at a 1:4 ratio. Bulk heterojunction solar cells prepared by using a TIPSAntBT:PCBM blend reach power conversion efficiencies as high as 1.4 %.


Expectations of Patients and Their Families After the Treatment of Substance Use Disorder.
Substance use disorders are economically and socially devastating to families and societies. Expectations of the patients and their families during the posttreatment phase of substance use disorder need to be emphasized to maintain a patient's sobriety and prevent relapse. The aim of this study was to examine the prediction power of personal and sociodemographic factors of patients and their families to treatment outcomes. A descriptive, correlational, cross-sectional design was used. Data were collected from 80 patients treated for substance use disorders from a major psychiatric hospital and their family members regarding social, health, and psychological expectations. A three-step multiple hierarchical regression analysis was used to predict the power of personal and sociodemographic characteristics of patients' and their families' expectations to treatment outcomes. Heroin use, codeine use, family education, and family support were significant predictors of rehabilitation expectation ( p < .05). Level of education and heroin use were predictors for lower levels of rehabilitation expectation, whereas family support and codeine use were indicators for higher scores of rehabilitation expectation. Emphasis should be given to expectations of the patient and their family through appropriate psychoeducation and enhanced understanding and partnership.


Response to hepatitis B vaccine in preterm babies.
A well-accepted vaccination schedule for preterm babies is not available. We therefore studied the response to hepatitis B vaccine in preterm babies. 60 babies born to HBsAg-negative mothers were studied. Group I (n=20) consisted of term babies with birth weight >2.5 Kg, group II (n=20) included preterm babies with birth weight between 1.8 and 2.49 Kg, and group III (n=20) included preterm babies with birth weight between 1.2 and 1.79 Kg. Mean gestational age in the three groups was 38.5 (1.1), 33.5 (1.4) and 32.7 (2.1) weeks, respectively. All babies received 3 doses (10 microg/0.5 mL) of a recombinant HBV vaccine within 3 days of birth, and at 6 weeks and 6 months of life. Anti-HBs levels were measured one month after the 2nd and 3rd doses each; the immune response was categorized as good responders (anti-HBs >100 mIU/mL, low responders (anti-HBs 10-100 mIU/mL) and non-responders (anti-HBs <10 mIU/mL). Good antibody response after the second dose was seen in 95% of babies in group I, 60% of those in group II and 10% of those in group III. This increased to 100%, 90% and 45%, respectively after the third dose. The response was influenced by gestational age (r=0.73); 94% of babies with gestational age 34-36 weeks attained good antibody response compared to only 55% of babies with gestational age of 31-33 weeks. Birth weight had no independent influence on the antibody response. The response to hepatitis B vaccine is influenced by gestational age. Hence, in preterm babies, it is advisable to check antibody titers one month after the third dose to assess the need for a booster dose.


In vitro antifungal activity of naphthoquinone derivatives.
In vitro antifungal activities of naphtoquinone-derivatives, which are constituents of Shikon, roots of Lithospermum erythrorhizon, were investigated against several fungal pathogens. When the biological activity of these compounds was tested against fungi, a wide range of sensitivity was recorded. Shikonin was found to have a stronger than fluconazole against yeast-like fungi: four-fold against Candida krusei (minimal inhibitory concentration (MIC); 4 microg/ml) and two-fold (MIC; 4 microg/ml) against Saccharomyces cerevisiae, though it showed the same potency as fluconazole against C. glabrata. Deoxyshikonin also exhibited four-fold stronger activity against C. krusei (MIC; 4 microg/mi) and three-fold (MIC; 2 microg/ml) stronger against S. cerevisiae. Acetylshikonin and beta-hydroxyisovaleryl shikonin showed lower activities against all fungal pathogens except for C. krusei compared with the standard. Against the filamentous fungus, Trichosporon cutaneum, all naphthoquinones were found to have a range of activity with lower potency than standard. This result provides a rational basis for the clinical use of shikon and shows the possibility of its use in medicinal treatment as an anti-inflammatory agent with antifungal activity.


Correlation between amplification of the gene for the epidermal growth factor receptor (EGFR), data from preoperative proton-MR-spectroscopy (1HMRS) and histomorphometric data of glioblastomas.
To investigate a correlation between preoperative data from proton-MR-spectroscopy (1HMRS), genomic alterations (epidermal growth growth factor receptor [EGFR] gene amplification) and histomorphometric data from glioblastomas. In surgical specimens from 18 patients with glioblastomas, the degree of amplification of the gene for EGFR was determined in the region with the largest Ki-67 proliferation index by differential polymerase chain reaction. Correlation analysis showed significant positive correlation between degree of EGFR gene amplification and choline and total creatine (CHO/TCR) ratio, indicating increased membrane turnover. Cases with a high EGFR/interferon ratio showed a tendency toward a low lipid peak, whereas cases with a low EGFR/interferon ratio showed a large variation of the lipid peak. Differences were observed regarding quantitative histomorphologic data of tumor cell nuclei, especially nuclear size and shape. Together with the EGFR/interferon ratio, these morphometric data provided a good reclassification of cases with low and with high values for both spectroscopic variables by means of cross-validated linear discriminant analysis. The results provide further evidence for the biologic significance of metabolic data from preoperative 1HMRS, because these metabolic data showed a significant statistical relationship with histomorphology and a frequently occurring molecular biologic alteration (EGFR gene amplification) in glioblastomas.


Six Weeks of Calorie Restriction Improves Body Composition and Lipid Profile in Obese and Overweight Former Athletes.
The aim of the study was to compare the impact of 6 weeks of reducing daily caloric intake by 20% of total daily energy expenditure (TDEE)-CRI vs. reducing daily caloric intake by 30% of TDEE-CRII on body mass reduction and insulin metabolism in former athletes. 94 males aged 35.7 ± 5.3 years, height 180.5 ± 4.1 cm, and body mass 96.82 ± 6.2 kg were randomly assigned to the CRI (n = 49) or CRII (n = 45) group. Thirty-one participants (18 subjects from CRI and 13 from CRII) resigned from the study. The effects of both diets on the body composition variables (body mass-BM; body fat-BF; fat free mass-FFM; muscle mass-MM; total body water-TBW), lipid profile (total lipids-TL; total cholesterol-TCh; HDL cholesterol-HDL; LDL cholesterol-LDL; triglycerides-TG), and glucose control variables (glucose-GL, insulin-I, HOMA-IR, insulin-like growth factor-1-IGF-1, leptin and adiponectin) were measured. After adhering to the CR I diet, significant differences were observed in FFM, MM and TG. After adhering to the CR II diet, significant differences were registered in tCh, TL and LDL. Both diets had a significant influence on leptin and adiponectin concentrations. Significant differences in FFM, MM, and tCh were observed between the CR I and CR II groups. At the end of the dietary intervention, significant differences in BF, FFM, MM and TBW were observed between the CR I and CR II groups. The 6 weeks of CR II diet appeared to be more effective in reducing BF and lipid profile and proved to be especially suitable for subjects with high body fat content and an elevated level of lipoproteins and cholesterol. Both reductive diets were effective in improving the levels of leptin and adiponectin in obese former athletes.


Effects of prolactin on follicular oestradiol production in the rat.
The effect of prolactin on follicular oestradiol production was studied in rat ovaries in which luteal tissue was absent. A silicone tube containing progesterone was implanted before first ovulation and removed 14 days later. This resulted in the presence of preovulatory follicles 2 days later and ovulation 60 h after removal of the implant. Prolactin concentrations were raised either by injection of purified prolactin or by implantation of pituitary tissue under the kidney capsule. Injections with 100 or 200 micrograms prolactin starting at the time of removal of the implant (16.00 h on day 0) had no effect on in-vitro oestradiol production by preovulatory follicles obtained on day 2 (day of pro-oestrus). However, implantation of two pituitary glands under the kidney capsule, 2 weeks before progesterone removal, resulted in significantly lower follicular oestradiol production, although ovulation was not inhibited. Lowering of serum prolactin by injections of bromocriptine resulted in an increased follicular oestradiol production. These results indicate that, in addition to its well-known luteotrophic effect, prolactin can have a direct inhibitory effect on follicular oestradiol production. This effect might contribute to the reduced fertility seen during hyperprolactinaemia.


Endurance training damages small airway epithelium in mice.
In athletes, airway inflammatory cells were found to be increased in induced sputum or bronchial biopsies. Most data were obtained after exposure to cold and dry air at rest or during exercise. Whether training affects epithelial and inflammatory cells in small airways is unknown. To test whether endurance training under standard environmental conditions causes epithelial damage and inflammation in the small airways of mice. Formalin-fixed, paraffin-embedded lung sections were obtained in sedentary (n = 14) and endurance-trained (n = 16) Swiss mice at baseline and after 15, 30, and 45 days of training. The following variables were assessed (morphometry and immunohistochemistry) in small airways (basement membrane length < 1 mm): (1) integrity, proliferation, and apoptosis of bronchiolar epithelium; and (2) infiltration, activation, and apoptosis of inflammatory cells. Compared with sedentary mice, bronchiolar epithelium of trained mice showed progressive loss of ciliated cells, slightly increased thickness, unchanged goblet cell number and appearance, and increased apoptosis and proliferation (proliferating cell nuclear antigen) (p < 0.001 for all variables). Leukocytes (CD45(+) cells) infiltrated airway walls (p < 0.0001) and accumulated within the lumen (p < 0.001); however, apoptosis of CD45(+) cells did not differ between trained and sedentary mice. Nuclear factor-kappaB translocation and inhibitor-alpha of NF-kappaB (IkappaBalpha) phosphorylation were not increased in trained compared with sedentary mice. Bronchiolar epithelium showed damage and repair associated with endurance training. Training increased inflammatory cells in small airways, but inflammatory activation was not increased. These changes may represent an adaptive response to increased ventilation during exercise.


A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals.
Intra-uterine growth restriction (IUGR) is a frequent disease, affecting up to 10% of human pregnancies and responsible for increased perinatal morbidity and mortality. Moreover, low birth weight is an important cause of the metabolic syndrome in the adult. Protein depletion during the gestation of rat females has been widely used as a model for human IUGR. By transcriptome analysis of control and protein-deprived rat placentas, we were able to identify 2543 transcripts modified more than 2.5 fold (1347 induced and 1196 repressed). Automatic functional classification enabled us to identify clusters of induced genes affecting chromosome structure, transcription, intracellular transport, protein modifications and apoptosis. In particular, we suggest the existence of a complex balance regulating apoptosis. Among repressed genes, we noted several groups of genes involved in immunity, signalling and degradation of noxious chemicals. These observations suggest that IUGR placentas have a decreased resistance to external aggression. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites. There was an over-representation of Zn finger (ZNF) proteins and Pdx1 (pancreatic and duodenal homeobox protein 1) putative binding sites. Consistently, Pdx1 and a high proportion of ZNF genes were induced at the transcriptional level. A similar analysis of ZNF promoters showed an increased presence of putative binding sites for the Tata box binding protein (Tbp). Consistently again, we showed that the Tbp and TBP-associated factors (Tafs) were up-regulated in IUGR placentas. Also, samples of human IUGR and control placentas showed that human orthologous ZNFs and PDX1 were transcriptionally induced, especially in non-vascular IUGR. Immunohistochemistry revealed increased expression of PDX1 in IUGR human placentas. In conclusion, our approach permitted the proposition of hypotheses on a hierarchy of gene inductions/repressions leading to massive transcriptional alterations in the IUGR placenta, in humans and in rodents.


Dexamethasone protects normal human liver cells from apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand by upregulating the expression of P-glycoproteins.
Glucocorticoids are effective for the treatment of acute-on-chronic pre-liver failure, severe chronic hepatitis B and acute liver failure; however, the mechanism underlying the effects of treatment by glucocorticoids remains to be fully elucidated. The role and detailed mechanism of how glucocorticoids prevent liver disease progression can be elucidated by investigating the apoptosis of hepatocytes following glucocorticoid treatment. P‑glycoproteins (P‑gps) also confer resistance to apoptosis induced by a diverse range of stimuli. Glucocorticoids, particularly dexamethasone (DEX), upregulate the expression of P‑gp in several tissues. In the present study, the normal human L‑02 liver cell line was used, and techniques, including immunocytochemistry, western blot analysis, flow cytometry and reverse transcription‑quantitative polymerase chain reaction analysis were used for determining the expression levels of P‑gps, and for evaluating the effect of DEX pretreatment on the expression of P‑gps. DEX (1‑10 µM) was added to the cell culture media and incubated for 24‑72 h. The results revealed that DEX upregulated the mRNA and protein levels of P‑gp in a dose‑ and time‑dependent manner. Subsequently, tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) was used for the induction of apoptosis in the cells, followed by a terminal deoxynucleotidyl transferase dUTP nick end labeling assay to assess the apoptotic stages. The results demonstrated that apoptosis in the group of cells, which were pre‑treated with DEX was significantly lower than that in the control group. Treatment with tariquidar, a P‑gp inhibitor, reduced the anti‑apoptotic effects of DEX. These results established that DEX protects normal human liver cells from TRAIL‑induced apoptosis by upregulating the expression of P-gp. These observations may be useful for elucidating the mechanism of DEX for preventing the progression of liver disease.


Cu(II) Coordination Polymer Inhibits Liver Cancer Development via Targeting BCL-2 Protein and Activating Apoptotic Pathway.
In the current study, a Cu(II) coordination polymer (CP) has been created in success with the solvothermal reaction between an asymmetrical rigid N-heterocyclic carboxylatic acid (HL) and Cu(NO3)2·3H2O in the existence of 1,3-H2bdc, the second assistant ligand (in which 1,3-H2bdc is benzene-1,3-dicarboxylic acid and HL is 1-(4-carboxylphenyl)-3-(prazin-2-yl)-1H-1,2,4-triazole), and the chemical composition of this compound is [Cu2(L)2(1,3-bdc)(H2O)2]n (1). In the biological aspect, we screened the antiproliferation activity of the Cu(II) coordination polymer on five kinds of human cancer cell lines. IC50 and MTT assay results indicated that complex 1 had a spectral antiproliferative activity against liver cancer cells, peculiarly on human HepG2 liver cancer cells. From the data of Annexin V-FITC/PI assay and ROS detection, we can find that complex 1 exerts an antitumor effect by inducing ROS generation and cell apoptosis. Caspase-3 and caspase-9 activity detection revealed that activation of caspase-3 and caspase-9 plays vital roles in HepG2 cell apoptosis. These outcomes indicate that 1 is an excellent compound in treating cancer.


Sex differences in flea infections among rodent hosts: is there a male bias?
Recognizing patterns of parasite distribution among wildlife hosts is of major importance due to growing risk of transmission of zoonotic diseases to humans. Thus, sex-dependent parasite distribution in higher vertebrates is extensively studied, and males are often found more parasitized than females. Male-biased parasitism may be the result of weaker immunocompetence of male hosts owing to the immunosuppressive effect of androgens. Moreover, larger hosts (males) may demonstrate higher parasite infestation levels than smaller individuals (females), as they constitute a better nutritional resource for parasites and provide them with a greater variety of niches. In the present work, we investigated sex-dependent patterns of flea distribution among three common rodent species (Apodemus agrarius, Apodemus flavicollis, and Myodes glareolus). We hypothesized that males have a higher flea infestation than females. We confirm male-biased parasitism in A. agrarius and M. glareolus, but not in A. flavicollis. Additionally, flea infestation increased with body mass in A. agrarius, but not in A. flavicollis and M. glareolus. The detected differences in parasite distribution among sexes are probably the result of immunosuppressive effects of androgens and spatial behavior of males.


Comparative metabonomics of differential hydrazine toxicity in the rat and mouse.
Interspecies variation between rats and mice has been studied for hydrazine toxicity using a novel metabonomics approach. Hydrazine hydrochloride was administered to male Sprague-Dawley rats (30 mg/kg, n = 10 and 90 mg/kg, n = 10) and male B6C3F mice (100 mg/kg, n = 8 and 250 mg/kg, n = 8) by oral gavage. In each species, the high dose was selected to produce the major histopathologic effect, hepatocellular lipid accumulation. Urine samples were collected at sequential time points up to 168 h post dose and analyzed by 1H NMR spectroscopy. The metabolites of hydrazine, namely diacetyl hydrazine and 1,4,5,6-tetrahydro-6-oxo-3-pyridazine carboxylic acid (THOPC), were detected in both the rat and mouse urine samples. Monoacetyl hydrazine was detected only in urine samples from the rat and its absence in the urine of the mouse was attributed to a higher activity of N-acetyl transferases in the mouse compared with the rat. Differential metabolic effects observed between the two species included elevated urinary beta-alanine, 3-D-hydroxybutyrate, citrulline, N-acetylcitrulline, and reduced trimethylamine-N-oxide excretion unique to the rat. Metabolic principal component (PC) trajectories highlighted the greater degree of toxic response in the rat. A data scaling method, scaled to maximum aligned and reduced trajectories (SMART) analysis, was used to remove the differences between the metabolic starting positions of the rat and mouse and varying magnitudes of effect, to facilitate comparison of the response geometries between the rat and mouse. Mice followed "biphasic" open PC trajectories, with incomplete recovery 7 days after dosing, whereas rats followed closed "hairpin" time profiles, indicating functional reversibility. The greater magnitude of metabolic effects observed in the rat was supported by the more pronounced effect on liver pathology in the rat when compared with the mouse.


The State of Perplexity During Management of Gall Bladder Malignancy in an Expectant Young Mother.
During pregnancy, diagnosed cancer causes a major disturbance in the life of a pregnant woman and her family. The advanced stage of illness requiring systemic treatment inevitably leads the treating practitioner, with two lives at risk, into an ethical dilemma. The unborn child can be affected by the application of cancer medication to the mother as it is exposed to fetotoxic drugs. On the other hand, withholding therapy to allow fetal maturity may make the disease of the mother metastatic. Gall bladder carcinoma is often diagnosed as an unresectable disease (metastatic or locally advanced) due to its nonspecific symptomatology and carries the worst prognosis of any gastrointestinal or hepatobiliary neoplasm. We report a case of locally advanced gall bladder cancer (GBC) diagnosed during late pregnancy wherein the mother opted to continue the pregnancy without any intervention. A review of literature has been done to investigate the role of female hormones in a pregnancy complicating GBC with emphasis on management dilemma and the associated pitfalls.


Nanostructured thermoelectric skutterudite Co(1-x)Ni(x)Sb3 alloys.
Nanostructured Ni-doped skutterudites Co(1-x)Ni(x)Sb3 (with x ranging from 0.01 to 0.09) were prepared by ball milling and direct-current induced hot press. It was found that the thermal conductivity was reduced due to strong electron-phonon scattering from Ni-doping as well as phonon scattering from the increased grain boundary of the nanostructures. A maximum dimensionless figure-of-merit of 0.7 was obtained in Co0.91Ni0.09Sb3 at 525 degrees C.


Urothelial carcinoma of the bladder in a pediatric patient.
Urothelial carcinoma of the bladder in children and adolescents is rare. The World Health Organization database has recorded approximately 80 patients under age 16 that have been diagnosed with papillary bladder tumour since 1968.1 We are reporting on our case of urothelial carcinoma diagnosed in a 14-year-old male who presented with painless gross hematuria.


Multistep role for actin in initial closure of the mesencephalic neural groove in the chick embryo.
In a previous study, we have demonstrated that initial closure of the mesencephalic neural groove in the chick embryo is different from neurulation elsewhere. The neural groove invaginates, the walls appose and make contact in a ventrodorsal direction, and subsequently separate ventrally, forming an incipient neural tube lumen, which finally widens into a definitive lumen. In this study, a role for actin in the processes of this initial mesencephalic closure is studied. Based on rhodamine-phalloidin-stained sections, three distinct actin distribution patterns emerged, and time-lapse video microscopy revealed cytochalasin-D-reversible neurulation movements. We propose that actin is involved in formation and stabilization of the neural groove hinge point, in invagination of dorsal neuroepithelial cells into the neural groove, in the origin of the incipient lumen and the reinforcement of adhesion of the dorsal neural folds, and finally in the development of a wide lumen. Such a multifunctional effect of actin microfilaments within a narrow time window and at specific sites has not been reported yet.


Cooperation between multiple microbial pattern recognition systems is important for host protection against the intracellular pathogen Legionella pneumophila.
Multiple pattern recognition systems have been shown to initiate innate immune responses to microbial pathogens. The degree to which these detection systems cooperate with each other to provide host protection is unknown. Here, we investigated the importance of several immune surveillance pathways in protecting mice against lethal infection by the intracellular pathogen Legionella pneumophila, the causative agent of a severe pneumonia called Legionnaires' disease. Rip2 and Naip5/NLRC4 signaling was found to contribute to the innate immune response generated against L. pneumophila in the lung. Elimination of Rip2 or Naip5/NLRC4 signaling in MyD88-deficient mice resulted in increased replication and dissemination of L. pneumophila and higher rates of mortality. Irradiated wild-type mice receiving bone marrow cells from pattern recognition receptor-deficient mice displayed L. pneumophila infection phenotypes similar to those of donor mice. Rip2 and Naip5/NLRC4 signaling provided additive effects in protecting MyD88-deficient mice from lethal infection by L. pneumophila, with the contribution of Naip5/NLRC4 being slightly greater than that of Rip2. Thus, activation of the Rip2, MyD88, and Naip5/NLRC4 signaling pathways triggers a coordinated and synergistic response that protects the host against lethal infection by L. pneumophila. These data provide new insight into how different pattern recognition systems interact functionally to generate innate immune responses that protect the host from lethal infection by activating cellular pathways that restrict intracellular replication of L. pneumophila and by recruiting to the site of infection additional phagocytes that eliminate extracellular bacteria.


In smiles we trust? Smiling in the context of antisocial and borderline personality pathology.
Research suggests that people behave more cooperatively towards those who smile and less cooperatively towards those with personality pathology. Here, we integrated these two lines of research to model the combined effects of smiles and personality pathology on trust. In two experiments, participants read vignettes portraying a person with either borderline personality disorder, antisocial personality disorder, or no personality pathology. These portrayals were paired with a brief video clip that showed a person with either a neutral expression or a smile. Participants then played a Trust game with the "person" presented using each vignette and video clip combination. In Experiment 1, rates of trust were lower in response to the borderline and antisocial personality disorder vignettes compared with the control vignette. Interestingly, the effect of smiles was dependent upon personality. Although participants were more trusting of smiling confederates portrayed as having borderline personality disorder or no pathology, they were less trusting of confederates portrayed as having antisocial personality disorder if they smiled. In Experiment 2, run with a second set of personality vignettes, rates of trust were lower in response to both personality disorder vignettes and higher in response to smiles with no significant interaction. Together, these results suggest that information regarding both the current emotional state as well as the personality traits of a partner are important for creating trust.


Basophil releasability in human hydatidosis.
We studied immunoglobulin E (IgE)- and non-IgE-mediated releasability in basophils from 31 patients with hydatidosis. Histamine release to non-IgE-dependent stimuli did not differ significantly between normal individuals and patients with hydatidosis. On the contrary, an increased histamine liberation was obtained by challenging basophils from hydatid patients with anti-human IgE. It is concluded that Echinococcus granulosus infection induces an enhanced sensitivity of basophils to IgE-dependent stimuli.


Carbamazepine-induced sinus node dysfunction.
Carbamazepine, a drug used for the treatment of epilepsy and neuralgias, may exert hazardous effects on the cardiac conduction system. We report such a case of symptomatic brady-arrhythmia occurring in a 43-years-old male while on therapy with carbamazepine. Additionally, a literature review is made of previous cases of carbamazepine-induced sinus mode, AV node and His-Purkinje conduction disturbances.


Acute torsion of a retroperitoneal renal transplant mimicking renal vein thrombosis.
When imaging a renal transplant, the combination of absent flow in the main renal vein and reversed diastolic flow in the intrarenal arteries is considered highly suggestive of renal vein thrombosis. We present a case of torsion of a transplant kidney presenting with identical findings. Renal transplant torsion in general is a rare entity, previously described only in intraperitoneally placed organs; this case is the first that we are aware of with torsion occurring in a retroperitoneally placed graft.


[Repeated occlusion of the intraperitoneal access port for intraperitoneal chemotherapy in a patient with gastric cancer with peritoneal dissemination].
A phase III clinical trial to evaluate the efficacy of combination chemotherapy with intraperitoneal administration of paclitaxel for gastric cancer with peritoneal metastasis has been ongoing in Japan. A male patient in his 50s who was diagnosed as having advanced gastric cancer with peritoneal metastasis was enrolled in this trial. The patient was assigned to receive a regimen of intravenous and intraperitoneal paclitaxel combined with S-1. Although an intraperitoneal access port had been implanted to provide access to the peritoneal cavity, tube obstruction occurred twice. Laparoscopic examination revealed that the tube in the abdominal cavity had been totally covered with the great omentum. Therefore, the intraperitoneal regimen was discontinued. Although intraperitoneal chemotherapy for the treatment of peritoneal dissemination in gastric cancer is promising, precaution should be taken to avoid tube obstruction, which is a complication of the intraperitoneal tube placement.


Liver damage after halothane anaesthesia: analysis of cases in Finnish hospitals in 1972-1981.
A retrospective questionnaire revealed 11 patients with halothane related liver disturbances in Finland in 1972-1981. Seven of the cases were regarded as obvious and two as probable halothane hepatitis (HH). Four patients suffered HH twice, and none of the cases had a fatal outcome. The speed of onset of icterus correlated with the number of halothane exposures, as did the increase in liver enzyme (ASAT, ALAT) activities and the increase in serum bilirubin concentration. Halothane anaesthesia is strictly contraindicated if a nondefinite icterus has appeared after a previous exposure to halothane. It should not be given if unclear fever or prolonged nausea have followed a previous exposure. No major adverse effects or organ toxicity connected with enflurane were found.


Entanglement distribution in the quantum symmetric simple exclusion process.
We study the probability distribution of entanglement in the quantum symmetric simple exclusion process, a model of fermions hopping with random Brownian amplitudes between neighboring sites. We consider a protocol where the system is initialized in a pure product state of M particles, and we focus on the late-time distribution of Rényi-q entropies for a subsystem of size ℓ. By means of a Coulomb gas approach from random matrix theory, we compute analytically the large-deviation function of the entropy in the thermodynamic limit. For q>1, we show that, depending on the value of the ratio ℓ/M, the entropy distribution displays either two or three distinct regimes, ranging from low to high entanglement. These are connected by points where the probability density features singularities in its third derivative, which can be understood in terms of a transition in the corresponding charge density of the Coulomb gas. Our analytic results are supported by numerical Monte Carlo simulations.


1D Chiral Enantiomer Lead-Free Perovskites Induced Chiralopical Activity and Photoelectric Response.
Chirality is a fascinating geometrical concept with widespread applications in biology, chemistry, and materials. Incorporating chirality into hybrid perovskite materials can induce novel physical properties (chiral optical activity, nonlinear optics, etc.). Hybrid lead-free or lead-substituted perovskite materials, as representatives of perovskites, have been widely used in fields such as photovoltaics, sensors, catalysis, and detectors. However, the successful introduction of chirality into hybrid lead-free perovskites, which can enable their potential applications in areas such as circularly polarized light photodetectors, memories, and spin transistors, remains a challenging research topic. Here, we synthesized two new chiral lead-free perovskites, [(R)-2-methylpiperazine][BiI5] and [(S)-2-methylpiperazine][BiI5]. The material possesses a perovskite structure with a one-dimensional (1D) arrangement, denoted as ABX5. This structure is composed of chiral cations, specifically methylpiperazine, and endless chains of [BiI3] along the a-axis. These chains are assembled from distorted coplanar [BiI5]2- octahedra. The testing results revealed that (R)-1 and (S)-1 have narrow band gaps (Eg-R = 2.016 eV, Eg-S = 1.964 eV), high photoelectric response, and long carrier lifetime [R = 4.94 μs (τ), S = 7.85 μs (τ)]. It is worth noting that 1D chiral lead-free perovskites (R)-1 and (S)-1, which are synthesized in this study with narrow band gaps, high photoelectric response, and long carrier lifetime, have the potential to serve as alternative materials for the perovskite layer in future iterations of lead-free perovskite solar cells. Moreover, this research will inspire the preparation of multifunctional, lead-free perovskites.


Seasonal changes in myoglobin content in muscles of hibernating Yakutian ground squirrels.
Myoglobin content in skeletal muscles of the Yakutian ground squirrel Citellus undulatus was measured during different periods of the annual life cycle: in active animals in summer, and in hibernating and awake animals in winter. It was found that the Mb content in winter, irrespective of the state of the animal (hibernating or awake), is 2.5-3-fold higher than in summer. Analysis of biochemical data available in the literature suggests that the increase in Mb content in winter is most probably related to a high oxygen demand of muscles at the first stage of arousal when the body temperature rises from 0 to 10-12 degrees C (non-shivering thermogenesis or thermoregulatory tonus). At this stage, the oxygen-dependent processes in muscles proceed under conditions of blocked peripheral blood flow and failure of anaerobic glycolysis.


Reduction of 1-methyl-1-nitrosourea-induced mammary gland carcinoma by in vivo application of immunostimulatory CpG motifs in Sprague-Dawley rats.
In the present work the role of 13-cis retinoic acid and CpG oligodeoxynucleotides (CpG-ODN) in a 1-methyl-1-nitrosourea (MNU)-induced mammary gland carcinoma animal model was investigated. Treatment with both components, applied either alone or in combination, induced a significant decrease of the tumour burden and the volume of tumours only in rats that received CpG-ODN (p = 0.046, compared to the MNU control group). The data indicate that the Th-1 biased immunostimulatory capacities of CpG motifs may play a significant role in induction of protective immune responses against mammary gland tumours in Sprague-Dawley rats.


Social Determinants of Adherence to COVID-19 Preventive Guidelines in Iran: A Qualitative Study.
Adherence to COVID-19 preventative guidelines may be influenced by a variety of factors at the individual, societal, and institutional levels. The current study sought to investigate the social factors of adherence to those preventive measures from the perspective of health professionals. In October 2020, we performed qualitative research in Tehran, Iran, using the directed content analysis method. For the preparation of our interview guide and data analysis, we employed the WHO conceptual framework of socioeconomic determinants of health. Semi-structured interviews were conducted with 15 health professionals and policymakers who were chosen using a purposive sampling approach. MAXQDA-18 software was used to analyze the data. The Goba and Lincoln criteria were used to assess the quality of the results. There are 23 subcategories and 9 categories, which include socio-economic and political context (unstable macroeconomic environment, poor management of the pandemic, media and knowledge transfer), cultural and social values (fatalism, cultural norms, value conflicts, social customs), socio-economic positions (livelihood conditions), social capital (social cohesion, low trust), living conditions (housing conditions), occupational conditions (precarious employment), individual characteristics (demographic characteristics, personality traits, COVID-19 knowledge, and attitude), psycho-social factors (normalization of the disease, social pressure, and stigma), and health system leadership (health system problems, not taking evidence-based decisions, non-comprehensive preventive guidelines, non-operational guidelines, inadequate executive committee) were obtained. To limit the new COVID-19 transmission, people must be encouraged to follow COVID-19 prevention instructions. Improving adherence to COVID-19 preventive guidelines necessitates dealing with the complexities of responding to social determinants of those guidelines. Increasing public health literacy and knowledge of COVID-19, informing people about the consequences of social interactions and cultural customs in the spread of COVID-19, strengthening regulatory lockdown laws, improving guarantees for adhering to preventive guidelines, providing easy access to preventive supplies, and strengthening financial support for households with precarious employment are all important.


Nonequilibrium quasiparticle distribution induced by Kondo defects.
It is shown that in resistive nanowires out of equilibrium containing either single- or two-channel Kondo impurities the distribution function f(E,U) obeys scaling behavior in terms of the quasiparticle energy E and the bias voltage U. The numerically calculated f(E,U) curves explain quantitatively recent experiments on Cu and Au nanowires. The systematics of the impurity concentration c(imp) extracted from the comparison between theory and results on various Cu and Au samples strongly suggests that in these systems the scaling arises from magnetic Kondo impurities.


Erectile dysfunction and testosterone deficiency as cardiovascular risk factors?
Graham Jackson introduced the concept that erectile dysfunction was a marker for undiagnosed cardiovascular disease and future events. Unfortunately this had had modest impact on CVD management as ED is not incorporated into current risk calculators. In this paper, we examine recent evidence as to whether ED should be upgraded to a risk factor, especially with the high predictive value in younger men. In the Princeton 3 guidelines, he recognised the important impact of testosterone deficiency (TD) on all-cause and cardiovascular mortality. Recent evidence suggests that testosterone therapy to target levels and for sufficient duration, reduces cardiovascular events. In this paper, we also produce a case for testosterone deficiency to be considered as an independent risk factor. The evidence for inclusion of both ED and TD may now be stronger than accepted risk factors and have the advantages of being easily assessed, being quantitative, symptomatic and clinically relevant, especially in younger men.


Research in practice: a process of collaboration and negotiation.
Because practice-research conflicts confront nurses and investigators in clinical settings, our department of nursing research section found the need for collaboration and negotiation to be the major characteristic of practice setting research. Moreover, in the process of collaboration and negotiation, a number of problems arise for which alternative solutions need to be considered and tried. These problems include risk taking, vested interest, the rights of research subjects, and the need to produce both scientific and practical knowledge. The challenges faced when conducting research in practice settings are only partially predictable and only partially resolvable, but they are always exciting. The potential contributions are considerable since the basic challenge is to produce relevant, accurate information for immediate practice decisions, as well as to construct design and analysis methods that allow the project to contribute to nursings' general body of knowledge.


Exploring factors associated with pain in hemodialysis patients: a multicenter cross-sectional study from Palestine.
Chronic kidney disease (CKD) is a rising medical concern around the world. End-stage kidney disease (ESKD) is the last stage of CKD stages that necessitates renal replacement therapy (RRT), such as hemodialysis (HD), which seems to be the most commonly used type. However, patients on HD still suffer from high mortality and morbidity rates compared to those who receive a kidney transplant. Therefore, we aimed in this study to assess the prevalence of pain among ESKD patients on HD, as well as to explore the factors that were associated with this complaint. We conducted a multicenter cross-sectional study in the West Bank, Palestine, between August and November 2018. We used questionnaire-based direct interviews with subjects. After reviewing previous studies in the field, we developed our questionnaire and included items on patients' social, demographic, and clinical characteristics, including dialysis-related data. It also contained the Brief Pain Inventory (BPI) to assess different aspects of pain symptoms. A convenience sampling technique was used to collect data. Of the 300 participants, 66.3 % reported having chronic pain. HD sessions themselves were the most commonly cited cause for pain (21.6 %). The most commonly cited site of pain was the upper and lower limbs (37.3 %). Paracetamol was the most frequently used pharmacotherapy for pain alleviation. Multiple regression analysis showed that BMI (p = 0.018), gender (p = 0.023), and the number of comorbidities (p < 0.001) were independently associated with pain severity score. Pain is a highly prevalent symptom among HD patients in Palestine. Subpopulations with higher pain severity include females, patients with higher BMI, and those with multiple comorbidities. Healthcare providers should routinely assess pain in HD patients as it is considered a significant concern. This would involve pain assessment and development of a treatment plan to improve clinical outcomes. The nephrology associations should also push for pain management in HD patients as a clinical and research priority to improve pain-related disability.


Adverse outcomes in patients with community acquired pneumonia discharged with clinical instability from Internal Medicine Department.
There are well established admission criteria for patients suffering from community-acquired pneumonia, yet the clinical tool for decision to discharge the hospitalized patient is lacking. Continuous pressure to reduce hospital expenditures can lead to a premature discharge of unstable patients. The current study assessed the impact of clinical instability at discharge on short-term outcomes. Demographic data, background disease, laboratory tests results and PORT score were assessed prospectively. On the last day of the hospitalization 7 physiological parameters of instability were evaluated. 60 d composite mortality and readmission rate was a primary outcome measure. Of the 373 patients, 22% were discharged with 1 or more instabilities, of whom 26.8% reached primary outcome within 60 d, compared to 8.2% of patients with no instabilities. 60 d death rate was 2.1% in the former group, compared to 14.6% in the unstable patients (p<0.001). Instability on discharge remained a significant prognosticator of adverse outcome (odds ratio 3.5; 95% CI 1.8-6.8) after adjustment for pneumonia severity and baseline comorbidity. We concluded that discharging an unstable patient hospitalized with pneumonia is associated with elevated risk of death or readmission within 60 d. Pneumonia guidelines should include objective criteria for judging patients' stability and promptness for discharge.


Postoperative immunochemotherapy (BCG + 5-FU) in advanced gastric cancer.
Three hundred and twenty-two patients with locally advanced (stages III and IVA) and disseminated (stage IVB) gastric cancer were included in a randomized trial to assess the effect of immunochemotherapy (BCG and 5-fluorouracil,5-FU). The survival of patients receiving chemoimmunotherapy was compared to chemotherapy (5-FU) or no further treatment (control) groups. Patients with stage III underwent radical surgery (subtotal or total resection), stage IVA palliative resection, while explorative laparotomy or bypass was performed in stage IVB. Patients with stage III and IVA receiving immunochemotherapy had significantly (p less than 0.05) prolonged survival in comparison to chemotherapy or control groups. Prolongation of survival was more pronounced in patients with diffuse type carcinoma than in patients with intestinal type of tumour according to Lauren's classification. The survival of patients receiving chemotherapy was somewhat shorter than that of the control group, but the differences were not statistically significant. There was no effect of either immunochemotherapy or chemotherapy in patients with stage IVB. No serious side effects of immunochemotherapy were noted. These results indicate that immunochemotherapy may be a safe form of adjuvant treatment in patients with operable gastric cancer.


The endocrown: a unique method for restoring endodontically treated teeth.
The endocrown is a ceramic restoration that combines a core and a crown into a single structure. This restoration can be useful for endodontically treated teeth, for which traditional crown preparation can be difficult. Although most of these restorations are fabricated using single-visit computer-aided design/computer-aided manufacturing technology, they can also be fabricated by a laboratory using traditional polyvinyl siloxane impressions. This article will review the concept of endocrowns and describe 3 clinical situations in which an endocrown was utilized for the restoration of a compromised endodontically treated tooth.


Standard specimens for stain calibration: application to Romanowsky-Giemsa staining.
Standardized specimens with reproducible staining properties were fabricated from extracts of biological objects (bovine liver, nucleoprotamine and defatted muscle). The standard specimens were stained with two formulations of the Romanowsky-Giemsa stain (RG), using the same azure B and eosin Y. One formulation used methanol and Sorensen's buffer and the other DMSO and Hepes buffer as solvents. The standard specimens were stained either in the composite stain or in the individual dyes dissolved in the same solvents and at the same concentration as the composite stain. Solution spectroscopy demonstrated different spectra for the two formulations with some wavelength regions varying by more than an order of magnitude. The RG spectra were also very different from those of the individual dyes dissolved at the RG concentration in the respective solvents. The stained standard specimens were analyzed by microspectrophotometry and were found to have spectra similar to those of cell smears. Furthermore, the standard specimens were shown to be a repeatable substrate for stain uptake. The transmitted light intensity from random fields of the same standardized specimen varied +/- 5%. When specimens were stained at the same time, the specimen-to-specimen variation depended on preparation conditions and the measurement wavelength, but was as good as +/- 5% for some conditions. The quantitative stain performance of both formulations was studied and compared. The standardized specimens provide a tool for the quantitative study of staining processes and specimen preparation procedures and for stain calibration.


Role of follow-on drugs and indications on the WHO Essential Drug List.
The World Health Organization's Essential Drug List (EDL) contains first-in-class drugs and subsequent class entrants (follow-on drugs) deemed necessary to combat diseases prevalent throughout the world, with a special emphasis on developing nations. The EDL also includes originally approved and follow-on indications. There are opposing views regarding the value of follow-on drugs and indications. Critics suggest many follow-on drugs and indications offer little or no benefit to patients. Advocates counter that follow-on drugs offer advantages in terms of improved effectiveness, compliance and patient satisfaction. In order to inform this debate on the value of follow-on drugs and indications we examined the numbers of follow-on drugs on the EDL and the extent to which follow-on indications are recommended. We identified all 312 drugs on the 14th edition of the EDL, omitting 72 non-pharmaceutical entities. For the 240 pharmaceutical entities we ascertained whether the Food and Drug Administration (FDA) had approved them, and, if so, when each was approved. We chose a validated therapeutic classification system - the United States Pharmacopeia's Model Guidelines for Medicare formulary management - in order to distinguish first-in-class and follow-on drugs on the EDL. Specifically, we selected the formulary key drug type as our benchmark therapeutic class. We assigned each EDL drug to a formulary key drug type. We defined first-in-class drugs as the first in each formulary key drug type, and follow-on drugs as all other drugs in each formulary key drug type. We identified follow-on indications by comparing WHO-listed indications with the original approved indication(s) by the FDA. Finally, we examined the therapeutic rating (priority vs. standard) given by the FDA to follow-on drugs on the EDL. Sixty-three per cent of the EDL drugs were follow-ons; 15% of the indications were follow-on indications. Fourteen drugs were listed in multiple WHO (sub) groupings; and 49% of follow-on drugs were given a priority rating by the FDA. In light of the fact that the EDL only includes drugs and indications deemed essential, the large number of follow-on drugs, follow-on indications, and priority-rated follow-on drugs on the EDL suggest their importance. From a public policy perspective, it may prove counterproductive to erect hurdles that impede follow-on research and development.