Potential roles of the RGMa-FAK-Ras pathway in hippocampal mossy fiber sprouting in the pentylenetetrazole kindling model.
Mossy fiber sprouting (MFS) is a unique feature of chronic epilepsy. However, the molecular signals underlying MFS are still unclear. The repulsive guidance molecule A (RGMa) appears to contribute to axon growth and axonal guidance, and may exert its biological effects by dephosphorylating focal adhesion kinase (FAK) at Tyr397, then regulating the activation of Ras. The objective of this study was to explore the expression patterns of RGMa, FAK (Tyr397) and Ras in epileptogenesis, and their correlation with MFS. The epileptic models were established by intraperitoneal pentylenetetrazole (PTZ) injection of Sprague‑Dawley rats. At 3 days and at 1, 2, 4 and 6 weeks after the first PTZ injection, Timm staining was scored at different time points in the CA3 region of the hippocampus and dentate gyrus. The protein levels of RGMa, FAK (Tyr397) and Ras were analyzed at different time points in the CA3 region of the hippocampus using immunofluorescence, immunohistochemistry and western blot analysis. Compared with the control (saline‑injected) group, the expression of RGMa in the CA3 area was significantly downregulated (P<0.05) from 3 days and still maintained the low expression at 6 weeks in the PTZ group. The expression of FAK (Tyr397) and Ras was upregulated (P<0.05) in the PTZ groups. The Timm score in the CA3 region was significantly higher than that in the control group at different time points and reached a peak at 4 weeks. In the CA3 region, no obvious distinction was observed at the different time points in the control group. To the best of our knowledge, these are the first results to indicate that the RGMa‑FAK‑Ras pathway may be involved in MFS and the development of temporal lobe epilepsy.


First Report of Bacterial Soft Rot Disease on Pak Choi (Brassica rapa subsp. chinensis) caused by Pectobacterium brasiliense in the United States.
Pak choi (Brassica rapa subsp. chinensis) is an important vegetable crop native to China, known for high water content and low caloric value, containing high quality of protein, carbohydrates, fiber, vitamins, minerals, and secondary plant metabolites (Acikgoz, 2016). A pak choi field (8,000 sq. ft.) on Oahu, Hawaii, was visited in May 2020. About 10% plants were infected and showed characteristic symptoms of soft rot, wet lesions, macerated infected stem and necrotic leaves (Figure1A-D); leading to the suspect of one of the most devastating bacterial pathogens within genus Pectobacterium (Boluk et al. 2020; Li et al. 2019; Arizala et al. 2020; Arizala and Arif, 2019). Four infected plants were collected from the field, and stems were surface sterilized with 0.6% sodium hypochlorite solution for 30 sec, followed by three consecutive rinses in distilled water. The stems were aseptically macerated, streaked on Crystal violet pectate medium (CVP) (Hélias et al. 2011), and incubated for 48 h at 26 ± 2°C. The peculiar morphological characteristic of pectolytic bacterial pathogen, forming pits on CVP, were observed (Meng et al. 2016) (Figure 1E). Purification of bacterial colonies were done by re-streaking of a single colony on dextrose peptone agar (DPA-without tetrazolium chloride; Norman and Alvarez 1989). DNA was isolated from bacterial cultures using the DNeasy Blood and Tissue Kit (Qiagen, Germantown, MA), respectively. Molecular identification of four strains (PL243-246) were performed by the sequencing region of the housekeeping gene dnaA (chromosomal replication initiation protein) using Pec. dnaA-F1/R1 primer set (Dobhal et al. 2020). The amplified PCR product was enzymatically cleaned using ExoSAP-ITTM (Affymetrix Inc, Santa Clara, CA), and sent for sequencing at the GENEWIZ facility (Genewiz, La Jolla, CA) using both forward and reverse primers. The dnaA gene sequences were aligned using Geneious, and manually edited to remove the errors. The consensus sequences were analyzed with the NCBI BLASTn tool and were deposited in the NCBI GenBank under the accession numbers MT899920-MT899923. The NCBI BLASTn report indicated that all the sequences shared 99-100% identity and query cover with Pectobacterium brasiliense accession numbers MN544627-29. A phylogenetic analysis, using Geneious, was performed with the dnaA sequences representing different Pectobacterium spp., all strains grouped within the clade of P. brasiliense (Figure 2; Arizala et al, 2020). A pathogenicity assay was carried out in three replications on pak choi grown in pots containing commercial pot mixture, and maintained in the controlled-greenhouse (temperature 26-30°C; relative humidity 50-58%). Three-weeks old plant stems were artificially inoculated with 100 µl bacterial suspensions of PL243 (1.3x 10⁸ CFU/ml), PL244 (1.2x 10⁸ CFU/ml), PL 245 (1.2x 10⁸ CFU/ml) and PL246 (1.1x 10⁸CFU/ml); control plants were inoculated with 100 µl of distilled water (Figure 1F). Two days after inoculation, the soft rot and wilting symptoms (Figure 1G-H), similar to the ones observed on the field, were developed for all four strains tested. Bacteria was successfully re-isolated from the inoculated plants; DNA was isolated, amplified, sequenced for dnaA region and analyzed for 100% homology with original strains, to fulfill Koch's postulates. Based on the molecular characteristics re-isolates were identical to the original strains. To the best of our knowledge, this is the first report of P. brasiliense on pak choi in the USA. Recent reports indicated that the pathogen could potentially pose a threat to cruciferous crops, therefore, highlighting a need to conduct a state-wide survey for pectinolytic bacteria, and implement better management strategies to combat the vegetable crop losses.


The interaction between abiotic photodegradation and microbial decomposition under ultraviolet radiation.
Elevated ultraviolet (UV) radiation has been demonstrated to stimulate litter decomposition. Despite years of research, it is still not fully understood whether the acceleration in litter degradation is primarily attributed to abiotic photodegradation or the combined effects of abiotic photodegradation and microbial decomposition. In this study, we used meta-analysis to synthesize photodegradation studies and compared the effects of UV radiation on litter decomposition between abiotic and biotic conditions. We also conducted a microcosm experiment to assess the effects of UV radiation on litter biodegradability and microbial activity. Overall, our meta-analysis found that under abiotic photodegradation, UV radiation reduced the remaining litter mass by 1.44% (95% CI: 0.85% to 2.08%), did not affect the remaining lignin and increased the dissolved organic carbon (DOC) concentration by 14.01% (1.49-23.67%). Under combined abiotic photodegradation and microbial decomposition, UV radiation reduced the remaining litter mass and lignin by 1.60% (0.04-3.58%) and 16.07% (9.27-24.23%), respectively, but did not alter DOC concentration. UV radiation had no significant impact on soil microbial biomass carbon (MBC), but it reduced microbial respiration by 44.91% (2.26-78.62%) and altered the composition of the microbial community. In addition, UV radiation reduced nitrogen (N) immobilization by 19.44% (4.77-37.92%). Our microcosm experiment further indicated that DOC concentration and the amount of respired C in UV-treated litter increased with UV exposure time, suggesting that longer UV exposure resulted in greater biodegradability. Overall, our study suggested that UV exposure could increase litter biodegradability by increasing the microbial accessibility of lignin, as well as the labile carbon supply to microbes. However, the remaining litter mass was not different between the abiotic and biotic conditions, most likely because the positive effect of UV radiation on litter biodegradability was offset by its negative effect on microbial activity. Our results also suggested that UV radiation could alter the N cycle during decomposition, primarily by inhibiting N immobilization.


Adenomatous polyposis coli (Apc) tumor suppressor gene as a multifunctional gene.
The adenomatous polyposis coli (Apc) gene is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. The Apc gene product (APC), basically a cytoplasmic protein, blocks cell cycle progression and plays crucial roles in development. The APC binds to beta-catenin, axin and glycogen synthase kinase 3beta to form a large protein complex, in which beta-catenin is phosphorylated and broken down, resulting in negative regulation of the Wnt signaling pathway. Most of the mutated Apc genes in colorectal tumors lack beta-catenin-binding regions and fail to inhibit Wnt signaling, leading to overproliferation of tumor cells. The APC, having some nuclear localizing signals in its molecule, can also be localized in the nucleus. The nuclear APC exports excess beta-catenin to the cytoplasm. Through its C-terminus, APC binds to post-synaptic density discs large zonula occludens domain-containing proteins, such as discs large (DLG) and post-synaptic density (PSD)-95, and may play important roles in epithelial morphogenesis, brain development and neuronal functions. In addition, APC is involved in cell motility through its association with microtubules and APC-stimulated guanine nucleotide exchange factor. Colocalization of APC and DLG is dependent on microtubules. The Apc gene is highly expressed in the embryonic and postnatal developing brain. Recently, we found that APC is required for the activity of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by facilitating the clustering of PSD-95 and these receptors at the postsynapse. In addition, APC is present in astrocytes, although its role in astrocytes is, as yet, unknown.


Post-diagnosis skin cancer follow-up in rural general practice: A mixed-method study.
The literature reveals a lack of consensus on recommendations for follow-up of skin cancer in general practice for all types of skin cancer. The objective of this paper was to evaluate post-treatment surveillance practices for both melanotic and non-melanotic skin cancers (NMSC) by general practitioners (GPs) in regional Victoria, and to identify challenges in follow-up for skin cancers in rural areas. A mixed-method study involving a survey and semi-structured interviews with GPs and registrars in Gippsland was carried out in 2015. The survey of 65 participants showed that 69% (45/65) followed up NMSC opportunistically, while 66% (43/65) reported using a structured follow-up practice for melanoma. Six practitioners from the interviews identified the patient's level of education, time constraints, practitioner accessibility and specialists' availability as some common challenges in follow-up. We recommend that rural GPs review follow-up strategies for all skin cancers, through the establishment of guidelines and a recall system.


[Dosimetric analysis of LINAC based stereotactic irradiation of brain tumours in CIRS SHANE phantom].
The aim of the study was to compare the different stereotactic treatment plans and dose calculation algorithms for small targets with film dosimetry in anthropomorphic phantom. Treatment plans were prepared for multiple targets with single setup isocenter. Plans for three different irradiation techniques were generated using conformal arc with four non-coplanar arcs, RapidArc with two coplanar full arcs and RapidArc with four non-coplanar arcs in the Varian Eclipse v13.7.16 TPS. Conformal arc and RapidArc plans were calculated using AAA, Acuros XBDm and XBDw algorithms. Conformity index, gradient index and dose maximum were calculated for all PTVs. All measurements were made on the Varian TrueBeam linear accelerator. Comparison between computed and measured dose distributions was performed with gamma evaluation criteria of 3%, 3 mm; 3%, 1 mm and 2%, 2 mm. According to our results, the Eclipse AAA and AXB algorithms provide accurate dose distributions for homogeneous cranial irradiation.


Effect of GHB-use and GHB-induced comas on dorsolateral prefrontal cortex functioning in humans.
Gamma-hydroxybutyric acid (GHB) is a recreational drug associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced comas. Working memory (WM) deficits have been reported in association with GHB use, and animal studies have shown that GHB induces oxidative stress in vulnerable WM-related brain areas such as the dorsolateral prefrontal cortex (DLPFC). However, the effects of chronic GHB use and multiple GHB-induced comas on WM-related brain function in humans remains unknown. We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users who never experienced GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants performed an n-back WM task during functional magnetic resonance imaging (fMRI) to probe DLPFC functioning. The GHB-Coma group had lower premorbid IQ (p = .006) than the GHB-NoComa group despite comparable age and education level. There were also group differences in the use of other drugs than GHB. Therefore, all group comparisons were adjusted for IQ and drug use other than GHB. Compared with the GHB-NoComa and the No-GHB groups, the GHB-Coma group showed increased activity in the right DLPFC (pSVC = 0.028) and increased functional connectivity of the right DLPFC with a cluster comprising the left anterior cingulate and medial frontal gyrus (pFWE = 0.003). No significant fMRI differences were observed between the GHB-NoComa and No-GHB groups. Due to technical problems, no behavioural data were collected. These results suggest that multiple GHB-induced comas, but not GHB-use per se, are associated with alterations in WM-related brain function. Public awareness campaigns are required to minimize the potential adverse effects induced by GHB recreational use, and especially GHB-induced comas, even if no immediate side effects are experienced.


Separation of ortho, meta and para isomers of methylmethcathinone (MMC) and methylethcathinone (MEC) using LC-ESI-MS/MS: Application to forensic serum samples.
Separation and identification of positional isomers is an important issue in forensic toxicology, particularly in the context of new psychoactive substances (NPS). Despite the structural similarity, positional isomers often show different pharmacological properties and thus can exhibit dramatic differences with respect to their toxicity. Additionally, besides these pharmacological and toxicological effects, the legal status is also of great importance. We present a sensitive and selective LC-MS/MS method to separate the ortho, meta and para isomers of methylmethcathinone (MMC) and methylethcathinone (MEC) using a core-shell biphenyl analytical column. Reliability of the method was confirmed under consideration of the validation parameters selectivity, linearity, accuracy and precision, analytical limits, processed sample stability, matrix effects and recovery. Linearity was demonstrated over the entire calibration range from 5 to 250ng/ml with the use of a 1/x2 weighting. Appropriate quantification and detection limits (LLOQ=5ng/ml, LOD<2ng/ml) could be achieved. Application of the method to real serum samples collected between June 2014 and August 2016 revealed the proof of a recent MMC or MEC consumption, respectively, in eight cases. Isomers of MMC could be detected in three of these eight cases, of which two were positive for 3-MMC and one was positive for 2-MMC. The other samples were tested positively for 3-MEC. In none of the samples 4-MMC, 2-MEC or 4-MEC could be detected. Only substances that were not governmentally controlled at that time could be detected, reflecting the rapid response of the recreational drug market to newly enacting drug laws.


Erratum: Vol. 65, No. 20.
In the MMWR report, "Possible Zika Virus Infection Among Pregnant Women - United States and Territories, May 2016," the following persons should be included in the Zika and Pregnancy Working Group: "Nina Ahmad, New York State Department of Health; Jennifer White, New York State Department of Health."


Analysis of protein S-acylation by gas chromatography-coupled mass spectrometry using purified proteins.
S-acylation, also known as palmitoylation, involves the attachment of acyl fatty acids to thiol groups of cysteine residues through a reversible thioester bond. Owing to its reversibility, S-acylation is important in regulation of diverse signaling cascades, including Ras-associated cancers in mammals, stress response and metabolic regulation. Here we describe a simple protocol for analysis of protein S-acylation using gas chromatography-coupled mass spectrometry. Analysis can be carried out with as little as 1 microg of purified protein and allows chemical identification and, potentially, quantification of the acyl moieties. The method is based on cleavage of the fatty acids from proteins by hydrogenation with platinum (IV) oxide. This causes an acid transesterification of the acyl groups, adding an ethyl group to the carboxyl head of the fatty acid. The addition of the ethyl group reduces the polarity of the fatty acids, allowing their efficient separation by gas chromatography.


Hot tea and juk: the institutional meaning of food for Chinese elders in an American nursing home.
This qualitative study describes how Chinese elders in an American nursing home perceived their food and mealtime experiences. Data collection included 20 meal observations and interviews with 7 residents, 9 family members, and 17 staff members. Field notes and interviews were coded and analyzed using an iterative approach similar to grounded theory. All participant groups described institutional food and meals as individualized, nutritious therapy for medical illnesses. Mealtimes lacked sociability and sharing, and although family members provided Chinese food, they did not eat with residents. Residents generally did not consider the institution's effort to provide an "Asian diet" of hot tea and juk (rice porridge) to be Chinese food. These findings suggest that, for these Chinese elders, the biomedicalized, individualized food service and mealtime caregiving practices stripped food of its meaning as a social, shared mealtime experience with family. Nursing professionals and researchers should understand that provision of culturally competent mealtime care for ethnic (Chinese) long-term care residents involves important food service practices in addition to kinds of food.


Illuminating the surface spin texture of the giant-Rashba quantum-well system Bi/Ag(111) by circularly polarized photoemission.
We have mapped out the spin texture of a Bi/Ag surface alloy prepared on a thin Ag film by circularly polarized angle-resolved photoemission spectroscopy. A term proportional to ∇·A in the interaction Hamiltonian gives rise to strong surface photoexcitation, which interferes with a Rashba contribution to yield a pronounced circular dichroic effect in Bi/Ag. The dipole transition, often taken to be the only important photoexcitation mechanism, is actually negligible. A parameter-free calculation yields a dichroic pattern in excellent agreement with experiment.


[Effect of translating water on vegetation at the lower reaches of Tarim river].
Due to human irrational resource exploit in recent 50 years, many environment problems have appeared at the lower reaches of Tarim River, the environment degradation of this region became seriously. In order to restore green corridor and improve the environment at the lower reaches of Tarim River, the project of transporting water to the lower reaches of Tarim River was carried out from June 14, 2000 and the water reached Taitema lake finally. After two years' monitoring and analyzing in this region, it was found that the ground-water level went up and much extremely degraded vegetation was restored. Some xerophytic arbor and bush restored obviously with the change of habitat. Correspondingly, the groundwater level, vegetation coverage, diversity of biology, the species richness and crown of Populus euphratica all changed. By the end of September 2002, the result showed that the respond range of the ground-water level was 800 m from the river, and the respond range of vegetation was not beyond 700 m at the middle part of lower reaches of Tarim River. Due to the different environmental factors in different parts at the lower reaches of Tarim River, the response range changed accordingly. In general, the respond range became smaller and smaller from the upriver part to downstream part.


An unusual presentation of intestinal duplication mimicking torsion of Meckel's diverticulum: a rare report of a pediatric case.
Enteric duplication is a congenital disease that occurs throughout the entire gastrointestinal tract. Although it may sometimes cause intestinal volvulus, a few reports have described cases of enteric duplication twisted on itself. We experienced a rare pediatric case of long-segment tubular ileal duplication showing torsion. Torsion of enteric duplication is extremely rare. We herein report a pediatric case showing unusual torsion of ileal duplication requiring emergency surgery. A 3-year-old boy presented with abdominal pain and vomiting. Contrast-enhanced computed tomography (CT) revealed a cystic luminal structure with a blind end and fluid collection in the pelvic cavity. CT also showed no findings of ileus or intestinal dilatation except for a cystic luminal structure. The preoperative diagnosis was torsion of Meckel's diverticulum. The patient underwent emergent explorative diagnostic laparoscopy. As a result, a necrotic luminal structure and bloody ascites were recognized, and small-scale laparotomy was performed. Long-segment ileal duplication was recognized. The long-segment tubular ileal duplication shared the anti-mesenteric side of the intestinal wall along one-third of its length. The residual two-thirds of its length was free from the ileum and its blind end was twisted in a manner that looked similar to Meckel's diverticulum. Normal ileum and the duplication, including the twisted necrotic portion, were resected, and ileal anastomosis was performed. The postoperative course was uneventful. A pathological examination confirmed the definitive diagnosis of enteric duplication. We reported the unusual presentation of intestinal duplication mimicking torsion of Meckel's diverticulum. Enteric duplication shows various clinical symptoms and presentations. We must understand that the classification of digestive enteric duplication is diverse with a variety of associated clinical symptoms.


[Significance of acute arthroscopy for the verification of fresh isolated cruciate ligament rupture].
Arthroscopy for diagnosis in isolated rupture of the cruciate ligaments of the knee. Arthroscopy of the knee was performed in the years 1981 through 1983 in 1107 patients, arthroscopic meniscectomy in 340 patients. In acute traumatic haemarthrosis of the knee 74 "isolated" ruptures of the cruciate ligaments were found. The exact disclosure of these 74 cases gave a real isolated rupture of the anterior cruciate in 28.4%, an isolated rupture combined with meniscus tears and connected with flake fracture each in 20.3%. In 17.5% the exact diagnosis was a disruption of the anterior cruciate together with meniscus tears and flake fracture. Acute arthroscopy allows a more accurate diagnosis of injury to joint structures. If there was an intraligamentary rupture of the anterior cruciate and meniscus tear or flake fracture we did arthroscopic meniscectomy and removed the small flake. The substitution of the anterior cruciate was performed, if there were instability complains, later on at agreeable time for the patient.


Readmission Diagnoses After Pediatric Severe Sepsis Hospitalization.
Severe sepsis is a significant cause of healthcare use and morbidity among pediatric patients, but little is known about readmission diagnoses. We sought to determine the most common readmission diagnoses after pediatric severe sepsis, the extent to which post-sepsis readmissions may be potentially preventable, and whether patterns of readmission diagnoses differ compared with readmissions after other common acute medical hospitalizations. Observational cohort study. National Readmission Database (2013-2014), including all-payer hospitalizations from 22 states. Four-thousand five-hundred twenty-eight pediatric severe sepsis hospitalizations, matched by age, gender, comorbidities, and length of stay to 4,528 pediatric hospitalizations for other common acute medical conditions. None. We compared rates of 30-day all cause, diagnosis-specific, and potentially preventable hospital readmissions using McNemar's chi-square tests for paired data. Among 5,841 eligible pediatric severe sepsis hospitalizations with live discharge, 4,528 (77.5%) were matched 1:1 to 4,528 pediatric hospitalizations for other acute medical conditions. Of 4,528 matched sepsis hospitalizations, 851 (18.8% [95% CI, 16.0-18.2]) were rehospitalized within 30 days, compared with 775 (17.1% [95% CI, 17.1-20.0]) of matched hospitalizations for other causes (p = 0.02). The most common readmission diagnoses were chemotherapy, device complications, and sepsis, all of which were several-fold higher after sepsis versus after matched nonsepsis hospitalization. Only 11.5% of readmissions were for ambulatory care sensitive conditions compared with 23% of rehospitalizations after common acute medical conditions. More than one in six children surviving severe sepsis were rehospitalized within 30 days, most commonly for maintenance chemotherapy, medical device complications, or recurrent sepsis. Only a small proportion of readmissions were for ambulatory care sensitive conditions.


Method for determining the solubilities of hydrophobic organics in subcritical water.
A rapid and simple method has been developed to determine the solubility of organic compounds in water at temperatures from 25 to 250 degrees C and with enough pressure to maintain the liquid state ("subcritical" water). Water is heated and then passed through a cell containing excess test solute. The water, now saturated with solute, is blended with chloroform, cooled, and collected, and the chloroform fraction is analyzed by gas chromatography. Replicate determinations have typical reproducibilities, indicated by the relative standard deviation, of < 5%. Solubilities at 25 degrees C determined by this method are in good agreement with published data. Increasing the temperature of water from 25 degrees C to near the normal melting point of the organic solute results in solubility enhancements ranging from 6-fold for naphthalene (at 65 vs 25 degrees C) to 130,000-fold for chlorothalonil (at 200 vs 25 degrees C).


ECD--a totally integrated database of Escherichia coli K12.
We have compiled the DNA sequence data for E. coli available from the GENBANK and EMBL data libraries and independently from the literature. Starting with this update of our Escherichia coli database (ECD release 20) we provide major changes compared to previous issues. This update not only represents another substantial increase in sequence information, it also allows now to find the exact physical location of each individual gene or regulatory region, even regarding discrepancies in nomenclature. In order to save space this printed version does not contain the database itself anymore, but we provide several examples. The complete database is publically available in electronic form together with a self explaining application program or as a flat file. The complete compilation including a full set of genetic map data and the E. coli protein index can be obtained in machine readable form from the EMBL data library as a part of the CD-ROM issue of the EMBL sequence database, released and updated every three months. After deletion of all detected overlaps a total of 2,878,364 individual bp is found to be determined till the end of June 1994. This corresponds to a total of 60.98% of the entire E. coli chromosome consisting of about 4,720 kbp. This number may actually be higher by 9161 bp derived from other strains of E. coli.


Changing strategies for organ transplantation in atypical haemolytic uraemic syndrome: a tertiary case series.
We present three cases of organ transplantation for atypical haemolytic uraemic syndrome secondary to complement factor H mutation: one isolated renal transplant; one previously reported isolated liver transplant; and one combined liver and kidney transplant. All three patients were treated prior to the licensing of eculizumab for this condition, and all have had favourable outcomes with maintenance of graft function for years following transplantation. We discuss the evolution of transplantation therapy for aHUS over the last two decades. Transplantation decision-making in aHUS has evolved over this time with expanding knowledge of pathophysiology and genetics, alongside refined plasma exchange and anticoagulation protocols and improved centre experience. Our cases demonstrate how individual patient factors within this heterogeneous condition also underlie transplantation decisions and outcomes. Whilst our cases demonstrate that transplantation in aHUS can be a successful long-term treatment providing good quality of life, worldwide experience has proven that most curative treatment for aHUS strategies represents significant risks. Whether new pharmacotherapies such as eculizumab will alter this risk is yet to be determined.


A novel mechanism of ion homeostasis and salt tolerance in yeast: the Hal4 and Hal5 protein kinases modulate the Trk1-Trk2 potassium transporter.
The regulation of intracellular ion concentrations is a fundamental property of living cells. Although many ion transporters have been identified, the systems that modulate their activity remain largely unknown. We have characterized two partially redundant genes from Saccharomyces cerevisiae, HAL4/SAT4 and HAL5, that encode homologous protein kinases implicated in the regulation of cation uptake. Overexpression of these genes increases the tolerance of yeast cells to sodium and lithium, whereas gene disruptions result in greater cation sensitivity. These phenotypic effects of the mutations correlate with changes in cation uptake and are dependent on a functional Trk1-Trk2 potassium transport system. In addition, hal4 hal5 and trk1 trk2 mutants exhibit similar phenotypes: (i) they are deficient in potassium uptake; (ii) their growth is sensitive to a variety of toxic cations, including lithium, sodium, calcium, tetramethylammonium, hygromycin B, and low pH; and (iii) they exhibit increased uptake of methylammonium, an indicator of membrane potential. These results suggest that the Hal4 and Hal5 protein kinases activate the Trk1-Trk2 potassium transporter, increasing the influx of potassium and decreasing the membrane potential. The resulting loss in electrical driving force reduces the uptake of toxic cations and improves salt tolerance. Our data support a role for regulation of membrane potential in adaptation to salt stress that is mediated by the Hal4 and Hal5 kinases.


Longitudinal Clinical and Patient-Reported Outcomes After Transversus Abdominis Release for Complex Hernia Repair With a Review of the Literature.
Posterior component separation with transversus abdominis release (TAR) enables medial myofascial flap advancement in complex abdominal wall reconstruction. Here, we add to a growing body of literature on TAR by assessing longitudinal clinical and patient-reported outcomes (PROs) after complex ventral hernia repair (VHR) with TAR. Adult patients undergoing VHR with TAR between 10/15/2015 and 1/15/2020 were retrospectively identified. Patients with parastomal hernias and <12 months of follow-up were excluded. Clinical outcomes and PROs were assessed. Fifty-six patients were included with a median age and body mass index of 60 and 30.8 kg/m2, respectively. The average hernia defect was 384 cm2 [IQR 205-471], and all patients had retromuscular mesh placed. The most common complications were delayed healing (19.6%) and seroma (14.3%). There were no cases of mesh infection or explantation. Previous hernia repair and concurrent panniculectomy were risk factors for developing complications (P < .05). One patient (1.8%) recurred at a median follow-up of 25.2 months [IQR 18.2-42.4]. Significant improvement in disease-specific PROs was maintained throughout the follow-up period (before to after P < .05). Transversus abdominis release is a safe and efficacious technique to achieve fascial closure and retromuscular mesh in the repair of complex hernia defects.


Etiology, clinical profile, gender identity and long-term follow up of patients with ambiguous genitalia in India.
There is little information on the profile of children with ambiguous genitalia in India. Presented here is an analysis of patients with ambiguous genitalia registered in a general endocrine clinic during the last 2 decades. Seventy-four patients (age 4 months to 36 years) were registered during this period. Fifty-two were more than 5 years old at the time of registration. Thirty-five were reared as females, 29 as males; nine children (4 months to 1 year old) were brought for sex assignment, and one (with epispadias) was brought for correction of urinary incontinence. Investigations revealed 28 patients with congenital adrenal hyperplasia, 14 dysgenetic male pseudohermaphroditism, ten true hermaphroditism, six partial androgen insensitivity, four castration and one epispadias. There were eight patients with perineal hypospadias with normal Leydig cell reserve (normal LH, FSH and testosterone response to LHRH). Sex of rearing and gender identity were concordant in all except the patients with perineal hypospadias with normal Leydig cell response. These observations support the theory that prenatal androgen exposure masculinizes the brain.


Commentary: The potential of sleep research to contribute to our understanding on antisocial behaviour - a reflection on Brown, Beardslee, Frick, Steinberg and Cauffman (2022).
A growing body of work indicates that sleep problems are associated with antisocial behaviour in young people. This opens up the opportunity for interventions that improve sleep to reduce antisocial behaviour. Brown et al. (2022) provide important new leads that can help to target interventions, highlighting that the relationship may be most relevant to aggressive offending and that it is consistent across adolescence and young adulthood. The within-individual design adopted in this study has a number of methodological strengths. This commentary evaluates the effectiveness of the approach in terms of accounting for confounding effects and addressing temporal ordering. Directions for future research to build on the target paper are considered.


Bobbling head in a young subject.
Bobble-head Doll Syndrome is a rare and unique movement disorder found in children. Clinically, it is characterized by a to and fro or side to side movement of the head at the frequency of 2 to 3 Hz. It is mostly associated with cystic lesions around the third ventricle, choroid plexus papilloma, aqueductal stenosis and other rare disorders. An eleven year old child presented in the outpatient department with continuous to and fro movement of the head and declining vision for the last one month. MRI Scan showed a large contrast-enhanced lesion in the region of the third ventricle along with gross hydrocephalus. Ventriculo-peritoneal shunt was inserted and the movements of the head disappeared completely. Bobble-head doll syndrome is a rare condition and therefore this case is presented and the literature reviewed.


Metastatic breast cancer: sequencing hormonal therapy and positioning of fulvestrant.
Fulvestrant, a novel estrogen receptor (ER) antagonist with no agonist effects, binds, blocks, and degrades the ER, thereby downregulating cellular ER levels, which in turn leads to reduced expression of the progesterone receptor. Due to this specific working mechanism, fulvestrant is an important addition to the armamentarium of endocrine agents in advanced breast cancer (ABC). Fulvestrant has been shown to be equally effective as the third-generation aromatase inhibitor (AI) anastrozole in postmenopausal patients with hormone-sensitive ABC progressing prior to tamoxifen. In another randomized phase III trial, it was shown that fulvestrant had similar efficacy to tamoxifen in the first-line treatment of postmenopausal women with hormone receptor-positive ABC. When comparing the side effects of fulvestrant with tamoxifen and anastrozole, it was shown that fulvestrant is well tolerated compared with these agents and is associated with a lower incidence of joint disorders. Clinical benefit on fulvestrant treatment after AI therapy has been reported in a substantial number of patients (28-46%). On the other hand, it was also shown that sensitivity to further endocrine therapy is retained following progression on first-line or second-line fulvestrant (57% and 46% clinical benefit, respectively). In conclusion, fulvestrant provides us with an additional endocrine treatment option making it possible to prolong the time that patients with ABC can be treated with endocrine therapy.


Design and synthesis of a novel photoaffinity probe for labelling EGF receptor tyrosine kinases.
The epidermal growth factor receptor (EGFR) and HER2 are two important tyrosine kinases that play crucial roles in signal transduction pathways that regulate numerous cellular functions including proliferation, differentiation, migration, and angiogenesis. In the past 20 years, many proteomic methods have emerged as powerful methods to evaluate proteins in biological processes and human disease states. Among them, activity-based protein profiling (ABPP) is one useful approach for the functional analysis of proteins. In this study, a novel photoaffinity probe 11 was designed and synthesised to assess the target profiling of the reactive group in the photoaffinity probe 11. Biological evaluation was performed, and the results showed that the novel photoaffinity probe binds to EGFR and HER2 proteins and it hits targets by the reactive group.


Four-dimensional fetal echocardiography with spatiotemporal image correlation (STIC): a systematic study of standard cardiac views assessed by different observers.
To test the agreement between observers and reproducibility of a technique to display standard cardiac views of the left and right ventricular outflow tracts from four-dimensional volume datasets acquired with Spatiotemporal Image Correlation (STIC). A technique was developed to obtain dynamic multiplanar images of the left ventricular outflow tract (LVOT) and right ventricular outflow tract (RVOT) from volume datasets acquired with STIC. Volume datasets were acquired from fetuses with normal cardiac anatomy. Twenty volume datasets of satisfactory quality were pre-selected by one investigator. The data was randomly assigned for a blinded review by two independent observers with previous experience in fetal echocardiography. Only one volume dataset was used for each fetus. After a training session, the observers obtained standardized cardiac views of the LVOT and RVOT, which were scored on a scale of 1 to 5, based on diagnostic value and image quality (1=unacceptable, 2=marginal, 3=acceptable, 4=good, and 5=excellent). Median scores and interquartile range, as well as inter- and intraobserver agreement were calculated for each view. The mean menstrual age at the time of volume acquisition was 25.5+/-4.5 weeks. Median scores (interquartile range) for LVOT images, obtained by the first and second observers, were 3.5 (2.25-5.00) and 4 (3.00-5.00), respectively. The median scores (interquartile range) for RVOT images obtained by the first and second observers were 3 (3.00-5.00) and 3 (2.00-4.00), respectively. The interobserver intraclass correlation coefficient for the LVOT was 0.693 (95% CI 0.380-0.822), and 0.696 (95% CI 0.382-0.866) for the RVOT. For the intraobserver agreement analysis, observer 1 gave higher scores to the LVOT the second time the volumes were analyzed [LVOT: 3.50 (2.25-5.00) vs. 5.00 (4.00-5.00, p=0.008)]. STIC can be reproducibly used to evaluate fetal cardiac outflow tracts by independent examiners. Slightly better image quality rating scores during the intraobserver variability trial suggests the presence of a learning curve for the manipulation and analysis of volume data obtained by STIC.


Expression of glycoprotein 90K in human malignant pleural mesothelioma: correlation with patient survival.
The expression of the tumour-associated glycoprotein 90K in patients with malignant pleural mesothelioma (MM) has not been described. This study used enzyme-linked immunoassay (ELISA) to measure 90K in pleural effusions (PEs) and sera from patients with MM (n=28), lung cancer (LC) (n=14) and benign pleural disease (BPD) (n=15). Immunohistochemistry was used to investigate 90K expression in MM and LC tissue sections. The expression of 90K was further evaluated in vitro by ELISA and western blot analysis of conditioned media and cellular extracts of MM, LC and normal human mesothelial (NHM) cell cultures. Finally, the relationships between 90K expression in MM and patient age and survival were studied. The mean 90K level was significantly higher (p<0.05) in PEs of MM patients (11.0+/-6.6 microg/ml) than in LC (6.1+/-3.2 microg/ml) or BPD (6.2+/-5.0 microg/ml) patients. Immunohistochemistry showed a positive reaction for 90K in MM biopsy sections and positive staining limited to inflammatory infiltrates in LC sections. The level of 90K was significantly higher in cell culture media of MM than of LC or NHM (p<0.001). Bands representing proteins with molecular weight of approximately 90 kDa were detected by western blot in MM cellular extracts. An inverse correlation between PE 90K levels and MM patient age (r=-0.45; p=0.017) and a positive correlation between serum 90K levels and MM patient survival (r=0.62; p=0.006) were detected by linear regression analysis. Kaplan-Meier univariate analysis showed increased survival probability for MM patients with serum 90K level >7.3 microg/ml (log rank, p<0.05). This is the first report in MM of the expression of 90K and of its potential diagnostic and prognostic application.


A highly regular hexapod structure of lead sulfide: solution synthesis and Raman spectroscopy.
A highly regular hexapod-like structure of PbS with six symmetric arms has been synthesized by a simple and mild chemical solution route. The hexapod-like PbS structure was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and high-resolution TEM (HRTEM). The results show that each arm is perpendicular to the other four, and opposite to the last one. The arms are about 0.3-0.6 microm long, which have about 40-60 nm tips and 150-200 nm base. And the arm shows an icicle-like structure and some clear steps, and grows along 100 directions. The most possible growth mechanism discussed herein is based on the characterization results. The Raman spectra of the hexapod-like PbS structure were investigated. The results show that our products are sensitive to the laser and can be photodegraded easily.


Anesthesia for Endoscopic Third Ventriculostomy in Children.
Neuroendoscopy has established itself as a routine neurosurgical procedure in pediatric population. To have an uneventful smooth perioperative course, it is important for anesthesiologist to know about the key steps, possible complications, and specific anesthetic requirements. Among neuroendoscopies, endoscopic third ventriculostomy is the commonly performed one.


[Ectopic Warthin's tumour in nasopharynx. Revision of one clinical case].
This is a case report of a 69-year-old male patient referred to the ENT out patients with right-sided epistaxis and hipoacusis. Fibroptic examination reveals a cystic lesion at the exit of the right eustachian. A CT scan is informed as a well delimited and rounded-shaped tumour compatible with lymphoma. Excisional biopsy by a nasal rigid endoscopy is practiced and the histology result is Warthin's tumour. The nasopharynx is a rather unusual location for this type of tumours, almost exclusive in origin of major salivary glands. It's highlighted the unforeseeable histological diagnosis in this particular anatomical region, where the clinical differential diagnosis is broad and the access difficult.


Radical Termination via β-Scission Enables Photoenzymatic Allylic Alkylation Using "Ene"-Reductases.
Allylations are practical transformations that forge C-C bonds while introducing an alkene for further chemical manipulations. Here, we report a photoenzymatic allylation of α-chloroamides with allyl silanes using flavin-dependent 'ene'-reductases (EREDs). An engineered ERED can catalyze annulative allylic alkylation to prepare 5, 6, and 7-membered lactams with high levels of enantioselectivity. Ultrafast transient absorption spectroscopy indicates that radical termination occurs via β-scission of the silyl group to afford a silyl radical, a distinct mechanism by comparison to traditional radical allylations involving allyl silanes. Moreover, this represents an alternative strategy for radical termination using EREDs. This mechanism was applied to intermolecular couplings involving allyl sulfones and silyl enol ethers. Overall, this method highlights the opportunity for EREDs to catalyze radical termination strategies beyond hydrogen atom transfer.


Contribution of community health workers to the treatment of common illnesses among under 5-year-olds in rural Uganda.
The control of malaria, pneumonia, and diarrhoea is important for the reduction in morbidity and mortality among children under 5 years. Uganda has adopted the Integrated Community Case Management strategy using Community Health Workers (CHWs) to address this challenge. The extent and trend of these three conditions managed by the CHWs are not well documented. This study was done to describe the epidemiology and trends of the three common illnesses treated by the CHWs in Bugoye Sub-County in rural Uganda. A retrospective review of monthly morbidity data for children less than 5 years of age for the period April 2014-December 2018 for CHWs in rural Bugoye Sub-County in Kasese district, Uganda was done. The total number reviewed was 18,430 records. The data were analysed using STATA version 14. In total male were 50.2% of the sample, pneumonia was the highest cause of illness among the infants (< 1 year), while malaria was the highest among the children 1 year-59 months. Infection with a single illness was the commonest recorded cause of presentation but there were some children recorded with multiple illnesses. All the CHWs were managing the three common illnesses among children under 5 years. The trend of the three common illnesses was changing from malaria to pneumonia being the commonest. Children aged 12-24 months and 25-59 months were at 2.1 times (95% CI 1.7-2.4) and 5.2 times (95% CI 4.6-5.9), respectively, more likely to get malaria but less likely to get pneumonia and diarrhoea. Community Health Workers in rural Uganda are contributing significantly to the management of all the three commonest illnesses among under-5 years-old children. The trend of the commonest illness is changing from malaria to pneumonia. Children under 1 year are at a higher risk of getting pneumonia and diarrhoea and at a lower risk of getting malaria.


The small molecule C-6 is selectively cytotoxic against breast cancer cells and its biological action is characterized by mitochondrial defects and endoplasmic reticulum stress.
The establishment of drug resistance following treatment with chemotherapeutics is strongly associated with poor clinical outcome in patients, and drugs that target chemoresistant tumors have the potential to increase patient survival. In an effort to identify biological pathways of chemoresistant breast cancers that can be targeted therapeutically, a small molecule screen utilizing metastatic patient-derived breast cancer cells was conducted; from this previous report, the cytotoxic small molecule, C-6, was identified for its ability to selectively kill aggressive breast cancer cells in a caspase-independent manner. Here, we describe the cellular and molecular pathways induced following C-6 treatment in both normal and breast cancer cell lines. Transcriptome analyses and protein expression experiments were used to measure endoplasmic reticulum (ER) stress following C-6 treatment. Studies utilizing transmission electron microscopy and metabolomic profiling were conducted to characterize mitochondrial morphology and function in C-6-treated cells. Oxygen consumption rates and oxidative stress were also measured in breast cancer and normal mammary epithelial cells following treatment with the small molecule. Finally, structural modifications were made to the molecule and potency and cancer selectivity were evaluated. Treatment with C-6 resulted in ER stress in both breast cancer cells and normal mammary epithelial cells. Gross morphological defects were observed in the mitochondria and these aberrations were associated with metabolic imbalances and a diminished capacity for respiration. Following treatment with C-6, oxidative stress was observed in three breast cancer cell lines but not in normal mammary epithelial cells. Finally, synthetic modifications made to the small molecule resulted in the identification of the structural components that contribute to C-6's cancer-selective phenotype. The data reported here implicate mitochondrial and ER stress as a component of C-6's biological activity and provide insight into non-apoptotic cell death mechanisms; targeting biological pathways that induce mitochondrial dysfunction and ER stress may offer new strategies for the development of therapeutics that are effective against chemoresistant breast cancers.


Secondary osteonecrosis of the knee as a part of long COVID-19 syndrome: a case series.
COVID-19 infection affects different organ systems with long-term sequelae, which has been termed as long COVID-19 syndrome. To the best of our knowledge, osteonecrosis of the knee as a part of long COVID-19 syndrome has not been documented. Corticosteroids are being used extensively in moderate and severe cases of COVID-19. We report two cases who developed osteonecrosis of the knee after being treated for COVID-19 infection. In our case series, the mean cumulative dose of prednisolone was 1156.5 mg (900-1413 mg), which is less than the cumulative dose reported in literature for osteonecrosis of the knee. In our case series, the patients developed symptomatic osteonecrosis at a mean interval of 73 days after initiation of steroid therapy, with the earliest presenting at 25 days. Early diagnosis of osteonecrosis of the knee on high clinical suspicion by MRI would help in early intervention with bisphosphonate therapy.


A new tuning fork-based instrument for oscillatory shear rheology of nano-confined liquids.
We present a new method to measure rheological response of liquids confined to nano-scale which exhibit a considerable slow-down in dynamics compared to bulk liquids. The method relies on using a tuning fork force sensor that has stiffness of 5.5 × 10(4) N/m to avoid thermal noise. Off-resonance operation ensures application of a range of shear frequencies. This range is higher than the inverse of the system's mechanical relaxation time and allows the measurement of nonlinear effects emerging due to significant "slow down" in dynamics upon confinement. We develop necessary mathematical modelling to quantify our measurements. The instrument is a step forward towards resolving the controversies about the nature of nano-confined liquids.


Increased frequency of circulating invariant natural killer T cells in malignant pleural mesothelioma patients.
Invariant natural killer T (iNKT) cells are a distinct subset of human T cells, which expresses an invariant T cell receptor Vα24 Jα18 and recognizes glycolipid antigens in the context of CD1d molecules. iNKT cells exert pivotal regulatory roles in many immune responses, including antitumor immune responses. Alterations in iNKT cell frequency, phenotype, and activation state have been reported in cancer patients. No data are available on the iNKT cells in malignant pleural mesothelioma (MPM), a rare, but very aggressive, malignancy of the pleura with a very poor prognosis. Here, we studied the frequency, phenotype, and cytokine profile of circulating iNKT cells in MPM patients, and correlated results with tumor histological types (epithelioid, sarcomatoid, biphasic) and clinical stages (I-III). We found that the iNKT cell frequency was significantly increased in MPM patients with epithelioid and sarcomatoid types in comparison with healthy volunteers (HV); only three biphasic mesotheliomas were available in this study, thus no conclusions can be drawn for this MPM type. The increased frequency significantly correlates with the clinical stage of tumor with the highest value at the stage III in both epithelioid and sarcomatoid subtypes. According to the histological types, we measured changes in the frequencies of CD4⁺ CD8⁺ (DP) and CD4⁻CD8⁻ (DN), but not in the cytokine profiles (IFN-γ/IL-4 expression). These results demonstrate that the frequency of iNKT cells is increased in MPM patients and that this increase correlates with MPM type and stage.


Lesbian motherhood and genetic choices.
Rhonda, a physician, and Clara, a registered nurse, have been lovers for the past 7 years. Both women are in their 30s, in good health, and financially stable. Clara has contacted Dr. Robinson, a highly regarded obstetrician and geneticist, with an unusual request. Clara is seeking to become pregnant by means of in vitro fertilization (IVF) with an embryo transfer (ET) technology. She proposes being implanted with ova harvested from her partner, Rhonda, and fertilized in vitro with donor sperm from a local medical-school sperm bank. Dr. Robinson explains the relatively low success rate involved in IVF and ET techniques and suggests artificial insemination of Clara's own ova. Clara and Rhonda understand the low success rates but are undeterred. Their mutual goal is not merely to have a child but to share in the maternity of their children. What ethical issues are raised by the plan Clara and Rhonda propose? What are Dr. Robinson's ethical responsibilities with respect to the request by Clara and Rhonda?


Efficacy of collagen and alginate hydrogels for the prevention of rat chondrocyte dedifferentiation.
Dedifferentiation of chondrocytes remains a major problem in cartilage tissue engineering. The development of hydrogels that can preserve chondrogenic phenotype and prevent chondrocyte dedifferentiation is a meaningful strategy to solve dedifferentiation problem of chondrocytes. In the present study, three gels were prepared (alginate gel (Alg gel), type I collagen gel (Col gel), and their combination gel (Alg/Col gel)), and the in vitro efficacy of chondrocytes culture while preserving their phenotypes was investigated. While Col gel became substantially contracted with time, the cells encapsulated in Alg gel preserved the shape over the culture period of 14 days. The mechanical and cell-associated contraction behaviors of Alg/Col gel were similar to those of Alg. The cells in Alg and Alg/Col gels exhibited round morphology, whereas those in Col gel became elongated (i.e. fibroblast-like) during cultures. The cells proliferated with time in all gels with the highest proliferation being attained in Col gel. The expression of chondrogenic genes, including SOX9, type II collagen, and aggrecan, was significantly up-regulated in Alg/Col gel and Col gel, particularly in Col gel. However, the chondrocyte dedifferentiation markers, type I collagen and alkaline phosphatase (ALP), were also expressed at significant levels in Col gel, which being contrasted with the events in Alg and Alg/Col gels. The current results suggest the cells cultured in hydrogels can express chondrocyte dedifferentiation markers as well as chondrocyte markers, which draws attention to choose proper hydrogels for chondrocyte-based cartilage tissue engineering.


Spontaneous re-eruption of intruded permanent incisors: five case reports.
This report presents 5 cases of intrusive luxation in immature permanent central incisors. The intruded incisors, with careful monitoring, were allowed to spontaneously re-erupt, which avoided the need to reposition the tooth either orthodontically or surgically. All of the teeth re-erupted spontaneously in a few months. The root development continued in all of the cases and all pulps remained vital. There were no other signs of pulpal and/or periapical pathology. It can be concluded that intruded immature permanent teeth can spontaneously re-erupt, conserve their vitality, and continue their root development without any surgical or orthodontic management.


Safety of a novel formulation of ibuprofen sodium compared with standard ibuprofen and placebo.
Ibuprofen (IBU) is an efficacious over-the-counter analgesic/antipyretic with adverse event (AE) rates comparable to placebo. IBU sodium (IBU(Na)) is a newer, more soluble form that is absorbed faster than standard IBU, leading to more rapid analgesia. Although its safety and tolerability are expected to be comparable to standard IBU, this has not yet been reported. Pooled analysis comparing the safety of single-dose IBU(Na) (512 mg; equivalent to 400 mg IBU free acid; n = 362) with standard IBU tablets (400 mg; n = 342) and placebo (n = 187) across five Phase III, randomized, placebo-controlled, double-blind studies evaluating IBU(Na) for treatment of postoperative dental pain, tension-type headache, or fever. Treatment-emergent AEs (TEAEs) occurred in 5% of cases in the IBU(Na) group (25 events), 6.4% of cases in the standard IBU group (41 events), and 10.2% of cases in the placebo group (31 events). The most frequent TEAEs were in the following Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes: gastrointestinal disorders (2.8, 3.2, and 5.9% for IBU(Na), standard IBU, and placebo, respectively), nervous system disorders (1.4, 3.5, and 3.7% for IBU(Na), standard IBU, and placebo, respectively), and general disorders and administration-site conditions (1.1, 1.5, and 2.1% for IBU(Na), standard IBU, and placebo, respectively). Nausea was the most common TEAE (2.5, 2.6, and 5.9% for IBU(Na), standard IBU, and placebo, respectively). Only two AEs were considered related to treatment: pruritus (n = 1, IBU(Na)) and nausea (n = 1, placebo). Of those subjects reporting ≥ 1 TEAE, 44.4, 36.4, and 89.5% of subjects in the IBU(Na), standard IBU, and placebo groups, respectively, received rescue medication. IBU(Na) has a favorable safety profile comparable to those of standard IBU tablets and placebo in single-dose studies evaluating analgesic or antipyretic efficacy. ClinicalTrials.gov Registry Numbers: Dental pain studies: NCT01098747 and NCT01216163; headache studies: NCT01077973 and NCT01362491; pyresis study: NCT01035346.


Paracanthal "One-Snip" Decompression in a Cadaver Model of Retrobulbar Hemorrhage.
The authors assess the effectiveness of a modified paracanthal or "one-snip" procedure compared with the traditional lateral canthotomy and inferior cantholysis in the reduction of intraocular pressure (IOP) and proptosis in a human cadaveric model of retrobulbar hemorrhage. This study comprised a comparative interventional study in a cadaveric model of retrobulbar hemorrhage. Six orbits of 3 fresh cadavers were included in the study. Baseline measurements of IOP and proptosis were recorded for all 6 orbits before and after simulation of retrobulbar hemorrhage as previously described. Right orbits (n = 3) underwent traditional lateral canthotomy and inferior cantholysis. Left orbits (n = 3) underwent modified paracanthal or "one-snip" procedure. The primary outcome measures were reduction in IOP and proptosis between the 2 techniques. Following lateral canthotomy and inferior cantholysis of each right orbit, the average IOP dropped to 14 mm Hg (range of 11-18 mm Hg), corresponding to a mean decrease of 32 mm Hg. Following the "one-snip" procedure of each left orbit, the average IOP dropped to 19 mm Hg with a range of 16 to 23 mm Hg, corresponding to a mean decrease of 22 mm Hg. There was no statistically significant difference in IOP reduction (p = 0.36) or proptosis reduction (p = 0.23) between the 2 treatment groups. Compared with traditional lateral canthotomy xand inferior cantholysis, the modified paracanthal or "one-snip" procedure is effective for IOP reduction and led to mild improvement of proptosis in a cadaveric model of retrobulbar hemorrhage. The authors hope this study helps improve orbital compartment syndrome outcomes by providing an option that more providers will feel comfortable performing and therefore decreasing time to surgical decompression.


Time-resolved mRNA and miRNA expression profiling reveals crucial coregulation of molecular pathways involved in epithelial-pneumococcal interactions.
Streptococcus pneumoniae is a major causative agent of pneumonia worldwide and its complex interaction with the lung epithelium has not been thoroughly characterized. In this study, we exploited both RNA-sequencing and microRNA (miRNA)-sequencing approaches to monitor the transcriptional changes in human lung alveolar epithelial cells infected by S. pneumoniae in a time-resolved manner. A total of 1330 differentially expressed (DE) genes and 45 DE miRNAs were identified in all comparisons during the infection process. Clustering analysis showed that all DE genes were grouped into six clusters, several of which were primarily involved in inflammatory or immune responses. In addition, target gene enrichment analyses identified 11 transcription factors that were predicted to link at least one of four clusters, revealing transcriptional coregulation of multiple processes or pathways by common transcription factors. Notably, pharmacological treatment suggested that phosphorylation of p65 is important for optimal transcriptional regulation of target genes in epithelial cells exposed to pathogens. Furthermore, network-based clustering analysis separated the DE genes negatively regulated by DE miRNAs into two functional modules (M1 and M2), with an enrichment in immune responses and apoptotic signaling pathways for M1. Integrated network analyses of potential regulatory interactions in M1 revealed that multiple DE genes related to immunity and apoptosis were regulated by multiple miRNAs, indicating the coordinated regulation of multiple genes by multiple miRNAs. In conclusion, time-series expression profiling of messenger RNA and miRNA provides a wealth of information for global transcriptional changes, and offers comprehensive insight into the molecular mechanisms underlying host-pathogen interactions.


Expression of soluble ligand- and antibody-binding extracellular domain of human muscle acetylcholine receptor alpha subunit in yeast Pichia pastoris. Role of glycosylation in alpha-bungarotoxin binding.
The N-terminal extracellular domain (amino acids 1-210; halpha-(1-210)) of the alpha subunit of the human muscle nicotinic acetylcholine receptor (AChR), bearing the binding sites for cholinergic ligands and the main immunogenic region, the major target for anti-AChR antibodies in patients with myasthenia gravis, was expressed in the yeast, Pichia pastoris. The recombinant protein was water-soluble and glycosylated, and fast protein liquid chromatography analysis showed it to be a monomer. halpha-(1-210) bound (125)I-alpha-bungarotoxin with a high affinity (K(d) = 5.1 +/- 2.4 nm), and this binding was blocked by unlabeled d-tubocurarine and gallamine (K(i) approximately 7.5 mm). Interestingly, (125)I-alpha-bungarotoxin binding was markedly impaired by in vitro deglycosylation of halpha-(1-210). Several monoclonal antibodies that show partial or strict conformation-dependent binding to the AChR were able to bind to halpha-(1-210), as did antibodies from a large proportion of myasthenic patients. These results suggest that the extracellular domain of the human AChR alpha subunit expressed in P. pastoris has an apparently near native conformation. The correct folding of the recombinant protein, together with its relatively high expression yield, makes it suitable for structural studies on the nicotinic acetylcholine receptor and for use as an autoantigen in myasthenia gravis studies.


Structure of the modified nucleoside Q isolated from Escherichia coli transfer ribonucleic acid. 7-(4,5-cis-Dihydroxy-1-cyclopenten-3-ylaminomethyl)-7-deazaguanosine.
The structure of the unknown modified nucleoside Q, which is present in the first position of the anticodons of Escherichia coli tRNA Tyr, tRNA His, tRNA Asn, tRNA Asp, is proposed to be 7-(4,5-cis-dihydroxy-1-cyclopenten-3-ylaminomethyl)-7-deazaguanosine (1). The structure of Q was deduced by means of its uv absorption, mass spectrometry, proton magnetic resonance spectroscopy, and studies of its chemical reactivity. The structure of Q is unique since it is a derivative of 7-deazaguanosine having cyclopentenediol in the side chain at the C-7 position. This is the first example of purine skeleton modification in a nucleoside from tRNA.


Malignant pleural mesothelioma forming a huge mediastinal mass and causing atrial fibrillation.
A patient with malignant pleural mesothelioma was admitted with atrial fibrillation. Chest computed tomography showed a huge mediastinal tumor adjacent to the heart. Autopsy revealed a 12×9.5-cm mediastinal mass involving the right lung, which distorted and stretched the myocardial sleeve surrounding the right inferior pulmonary vein. This case demonstrates that advanced malignant pleural mesothelioma can cause atrial fibrillation, possibly by stimulating myocardium around a pulmonary vein.


The impact of gastroesophageal reflux disease on health-related quality of life.
Gastroesophageal reflux disease (GERD) affects health-related quality of life. We enrolled 533 adults with a history of heartburn symptoms for at least 6 months of moderate to severe heartburn in 4 of the 7 days before study entry. Patients were treated with ranitidine 150 mg twice a day for 6 weeks and Gelusil antacid tablets as needed. We measured physician-rated symptoms and the Medical Outcomes Study short-form 36 (SF-36) Health Survey at baseline and after 6 weeks of treatment. Baseline results were compared with normative data for the US population and for patients with selected chronic diseases. Treatment response was defined as no episode of moderate to severe heartburn for 7 days. Statistical significance was set at P <0.001. GERD patients reported significantly worse scores on all 8 SF-36 scales, physical function and well-being, and emotional well-being compared with the general population. Patients with GERD reported worse emotional well-being than patients with diabetes or hypertension. Treatment responders demonstrated significantly less pain and better physical function, social function, vitality, and emotional well-being compared with nonresponders. Patients with GERD experience decrements in health-related quality of life compared with the general population. The impact of GERD is most striking on measures of pain, mental health, and social function. Successful treatment for GERD results in improvements in health-related quality of life.


Non-IID Federated Learning With Sharper Risk Bound.
In federated learning (FL), the not independently or identically distributed (non-IID) data partitioning impairs the performance of the global model, which is a severe problem to be solved. Despite the extensive literature related to the algorithmic novelties and optimization analysis of FL, there has been relatively little theoretical research devoted to studying the generalization performance of non-IID FL. The generalization research of non-IID FL still lack effective tools and analytical approach. In this article, we propose weighted local Rademacher complexity to pertinently analyze the generalization properties of non-IID FL and derive a sharper excess risk bound based on weighted local Rademacher complexity, where the convergence rate is much faster than the existing bounds. Based on the theoretical results, we present a general framework federated averaging with local rademacher complexity (FedALRC) to lower the excess risk without additional communication costs compared to some famous methods, such as FedAvg. Through extensive experiments, we show that FedALRC outperforms FedAvg, FedProx and FedNova, and those experimental results coincide with our theoretical findings.


Interleukin-2 receptor in peripheral blood lymphocytes of Alzheimer's disease patients.
In this study, we investigated the differences in the incidence rate of human leukocyte antigen-DR (HLA-DR) and interleukin 2 receptor (IL-2R) in the peripheral blood lymphocytes of 13 women who were diagnosed clinically as having Alzheimer's disease (AD group), and 13 healthy women with no mental disorders (control group). As a result, the AD group showed a markedly higher rate of lymphocyte subsets of CD4+HLA-DR+, CD4+IL-2R+, CD8+HLA-DR+, CD8-HLA-DR+ and CD8+IL-2R+. This finding indicates a possible immune reaction occurring in the peripheral blood of AD patients. In addition, these higher rates correlate well with the changes in the immune system reported in the postmortem brains of AD patients. Our findings indicate that immunological interactions exist between the central nervous system and the peripheral blood lymphocytes of AD patients, and AD might be induced by an immune reaction occurring in the brain.


Protective Effects of Total Alkaloids from Menispermum dauricum against Airway Inflammation in Asthmatic Mice.
Menispermum dauricum is widely used to treat respiratory inflammation, including laryngopharyngitis, tonsillitis, tracheitis, and bronchitis. Total alkaloids isolated from M. dauricum have shown a variety of beneficial bioactivities. However, available data on the effects of M. dauricum total alkaloids against allergic asthma has not been reported. In present study, the protective effect of M. dauricum total alkaloids was evaluated by using an ovalbumin-induced in vivo model of asthma. The asthma model was prepared by sensitizing and challenging mice with ovalbumin, and M. dauricum total alkaloids (100, 200, and 400 mg/kg) were administrated to asthmatic mice by gavage. Histopathological analysis of pulmonary changes was detected by hematoxylin and eosin, and periodic acid-schiff staining. Inflammatory cell counts were determined in bronchoalveolar lavage fluid. Total immunoglobulin E and ovalbumin-specific immunoglobulin E levels in serum, and T-helper 2 cytokines and chemokine levels in bronchoalveolar lavage fluid were detected by an ELISA. Histological results demonstrated that M. dauricum total alkaloids significantly attenuated pulmonary inflammation in asthmatic mice. M. dauricum total alkaloid treatment exhibited marked effects on asthmatic mice in reducing inflammatory cell counts, decreasing interleukin-4, interleukin-5, and interleukin-13 concentrations, and downregulating TNF-α and eotaxin levels in bronchoalveolar lavage fluid. In addition, M. dauricum total alkaloids could also inhibit the elevated serum levels of total immunoglobulin E and ovalbumin-specific immunoglobulin E. These findings confirmed that M. dauricum total alkaloids could suppress airway inflammation in ovalbumin-induced asthma through regulating the T-helper 2 response and chemokine level. M. dauricum total alkaloids may be a potential ethnopharmacological agent for asthmatic patients.


Reward and relief dimensions of temptation to drink: construct validity and role in predicting differential benefit from acamprosate and naltrexone.
Researchers have sought to distinguish between individuals whose alcohol use disorder (AUD) is maintained by drinking to relieve negative affect ('relief drinkers') and those whose AUD is maintained by the rewarding effects of alcohol ('reward drinkers'). As an opioid receptor antagonist, naltrexone may be particularly effective for reward drinkers. Acamprosate, which has been shown to down-regulate the glutamatergic system, may be particularly effective for relief drinkers. This study sought to replicate and extend prior work (PREDICT study; Glöckner-Rist et al. ) by examining dimensions of reward and relief temptation to drink and subtypes of individuals with distinct patterns of reward/relief temptation. We utilized data from two randomized clinical trials for AUD (Project MATCH, n = 1726 and COMBINE study, n = 1383). We also tested whether classes of reward/relief temptation would predict differential response to naltrexone and acamprosate in COMBINE. Results replicated prior work by identifying reward and relief temptation factors, which had excellent reliability and construct validity. Using factor mixture modeling, we identified five distinct classes of reward/relief temptation that replicated across studies. In COMBINE, we found a significant class-by-acamprosate interaction effect. Among those most likely classified in the high relief/moderate reward temptation class, individuals had better drinking outcomes if assigned to acamprosate versus placebo. We did not find a significant class-by-naltrexone interaction effect. Our study questions the orthogonal classification of drinkers into only two types (reward or relief drinkers) and adds to the body of research on moderators of acamprosate, which may inform clinical decision making in the treatment of AUD.


Progression of coronary artery disease in non-ischemic dilated cardiomyopathy.
Dilated cardiomyopathy (DCM) is traditionally divided into ischemic and non-ischemic etiologies. We review data from clinical trials that suggest some patients in the latter subgroup develop ischemic complications including fatal myocardial infarction. However, the reasons for and magnitude of the effect are not known. Prospective screening studies and improved endpoint adjudication in clinical trials may be required to better delineate the degree to which the phenomenon occurs. Risk factor modification strategies should be applied to the non-ischemic DCM cohort, especially with continued improvements in survival rates in patients with heart failure.


Apocrine hidrocystoma of the foreskin. A case report and review of the literature.
Apocrine hidrocystoma (AH) is an uncommon benign cystic tumor that is rarely located in the genitalia. We present the case of a 52-year-old uncircumcised man who presented an AH on his foreskin. The lesion was non-proliferative. Including the present report, only 10 cases of penile AH have been published to date. Most patients are adult (mean age 39.2 years, range 25-56 years) and only one case in one child and another case in one adolescent have been reported. The lesion involves more commonly the foreskin followed by the shaft. The average maximum diameter was 1.6 cm (range 0.3-3 cm). The majority (70%) of tumors are unilocular. The main differential diagnosis of AH includes eccrine hidrocystoma, epidermal inclusion cyst and male median raphe cyst. Complete excision of the lesion is curative.


VARIANTS OF HERPES SIMPLEX VIRUS: ISOLATION, CHARACTERIZATION, AND FACTORS INFLUENCING PLAQUE FORMATION.
Rapp, Fred (Baylor University College of Medicine, Houston, Tex.). Variants of herpes simplex virus: isolation, characterization, and factors influencing plaque formation. J. Bacteriol. 86:985-991. 1963.-Variants of herpes simplex virus were isolated which differed in plaque size and in virulence for rabbits and mice. Keratitis on the rabbit cornea and generalized disease were associated with the large, but not the small, plaque variants. The large plaque variants were about as neurovirulent as was the parent strain for weanling mice, but the majority of the small plaque variants were only 1% as virulent for mice as was the parent virus. Agar inhibited the formation of plaques by the parent strain and all variants tested; development of plaques was retarded and the number of plaques was approximately 60% less than those developing under an overlay in which methyl cellulose had been substituted for the agar. Rabbit kidney cells and human embryonic lung fibroblasts were more sensitive than mouse embryo fibrolasts to infection with all variants tested.


S. epidermidis biofilm formation: effects of biomaterial surface chemistry and serum proteins.
Most infections due to implanted cardiovascular biomaterials are initiated by bacterial adhesion of Staphylococcus epidermidis, followed by colonization and biofilm formation on the surface of the implant. This study examined the role of serum proteins and material surface chemistry in the formation of S. epidermidis biofilm on polyurethanes (Elasthane 80A, hydrophobic) modified with polyethylene oxide (Elasthane 80A-6PEO, hydrophilic) and fluorocarbon (Elasthane 80A-6F, hydrophobic). Initial adhesion, aggregation, biofilm thickness, viability, and slime formation of S. epidermidis strain, RP62A in phosphate buffered saline (PBS), tryptic soy broth (TBS), and 20% pooled human serum was quantified. In the presence of adsorbed serum proteins, initial bacterial adhesion was suppressed significantly to <2% relative to adhesion in TSB or PBS. However, adhesion, aggregation, and proliferation increased dramatically in the 12-24 h period on Elasthane 80A and Elasthane 80A-6F, which resulted in an extensive network of biofilm. A contrasting trend was observed on the hydrophilic Elasthane 80A-6PEO surface, with minimal bacterial adhesion, which decreased steadily over 24 h. In the presence of serum proteins, an increasingly thick ( approximately 20 mum) biofilm formed on the hydrophobic surfaces over 48 h whereas the formation of a mature biofilm on the hydrophilic surface was impeded with few viable bacteria present over 48 h. Furthermore, slime was detected during the initial phase of bacterial adhesion at 2 h and increased over time with the formation of biofilm. These results have shown that while initial S. epidermidis adhesion is suppressed in the presence of adsorbed proteins, inter-bacterial adhesion possibly aided by slime production leads to the formation of a robust mature biofilm. Also, biomaterial surface chemistry affected biofilm formation and, most notably, polyethylene oxide significantly inhibited S. epidermidis biofilm formation over 48 h in vitro.


Response to selection for hatchability in turkeys at three altitudes.
Eggs from a commerical flock of Small White turkeys established at 76 meters above sea level were used to develop five lines of turkeys. Hatchability of fertile eggs was the only criterion used to establish selected lines at 76, 1524, and 2182 meters. Control lines were maintained at the 76 and 1524-meter locations. The objective of this study was to evaluate effects of the selection program on organ weights, body weight, and packed cell volumes (PCV). For two generations, eggs from one hatch at each of the three elevations were divided into three groups, two of which were exchanged for hatching and rearing. Twenty poults from the five lines at all three locations were sacrificed at 1-day, 2-weeks, and 4-weeks of age. Heart. liver spleen, adrenals, pancreas, lungs, kidneys, and gonads were removed, weighed, and the weight expressed as a percent of body weight. Blood samples were collected and PCV values determined at ages 1-day, 2-weeks, and 4-weeks at the 1524-meter elevation. Selection for hatchability had no adverse effect upon 1-day, 2, and 4-week body weights. Variations in body weight between locations were not due to natural environmental conditions, but rather to variations in management. Selection for hatchability coupled with natural selection resulted in the development of lines of turkeys with higher PCV values than the original control population. Exposure of turkey poults from the five genetic lines developed at an altitude of 2182 meters lead to an increase in relative weights of the heart and adrenal glands compared to birds at the 76 and 1524-meter locations. Exposure at the 2182-meter location also resulted in lighter spleens, pancreata, kidneys, and ovaries compared to birds at the 76 and 1524-meter locations. Selection for hatchability favors larger adrenals, livers, pancreata, kidneys, and lungs, but smaller hearts. Natural selection at higher elevations compounds the situation by favoring smaller adrenals and livers, but larger spleens, pancreata, and kidneys.


Next-generation sequencing of the whole mitochondrial genome identifies novel and common variants in patients with psoriasis, type 2 diabetes mellitus and psoriasis with comorbid type 2 diabetes mellitus.
Recent studies have shown the role of mitochondrial DNA (mtDNA) variants in the pathogenesis of both psoriasis (Ps) and type 2 diabetes (T2D) amongst different ethnicities. However, no studies have investigated the mtDNA variants present in patients with Ps, T2D, and both Ps and T2D (Ps-T2D) in the Arab population. The entire mitochondrial genomes of Kuwaiti subjects with Ps, T2D, Ps-T2D and healthy controls were sequenced using Ion Torrent next-generation sequencing. A total of 36 novel mutations and 51 previously reported mutations were identified in the patient groups that were absent in the controls. Amongst the novel mutations, eight were non-synonymous and exhibited amino acid changes. Of these, two missense mutations (G5262A and A12397G) in the ND genes were detected in the Ps group and a C15735T missense mutation in the CYB gene was detected in Ps-T2D. Other known sequence variations were seen more frequently in all or certain patient groups compared with the controls (P<0.05). Additionally, the A8701G missense mutation in the ATPase 6 gene missense mutation was also observed in a higher frequency in the Ps group compared with the control. The present study is the first to perform a complete mitochondrial genome sequence analysis of Kuwaiti subjects with Ps, T2D and Ps-T2D, and both novel and known mtDNA variants were discovered. The patient-specific novel non-synonymous mutations may be co-responsible in the determination of these diseases. The higher frequency of certain mtDNA variants in the patients compared with the controls may suggest a role in predisposing patients to these diseases. Further functional analyses are required to reveal the role of the identified mutations in these disease conditions.


Effects of at-school victimization and sexual orientation on lesbian, gay, or bisexual youths' health risk behavior.
To examine the link between victimization at school and health risk behaviors using representative data comparing lesbian, gay, and bisexual (LGB) youths and heterosexual youths. Data from the 1995 Youth Risk Behavior Survey taken in Massachusetts and Vermont were examined. This sample included 9188 9th through 12th grade students; 315 of these students were identified as LGB. Analyses of variance were used to examine health risk behaviors by sexual orientation by gender by victimization level. The combined effect of LGB status and high levels of at-school victimization was associated with the highest levels of health risk behaviors. LGB youths reporting high levels of at-school victimization reported higher levels of substance use, suicidality, and sexual risk behaviors than heterosexual peers reporting high levels of at-school victimization. Also, LGB youths reporting low levels of at-school victimization reported levels of substance use, suicidality, and sexual-risk behaviors that were similar to heterosexual peers who reported low at-school victimization. The findings provide evidence that differences in health risks among LGB youth are mediated by victimization at school. Such victimization of LGB youth is associated with health risk behaviors.


Ricerca scientifica ed educazione ambientale: l'approccio partecipativo dei progetti MAPS-MI nelle scuole di Milano.
The accumulated scientific evidence regarding the effects of air pollution on health calls for urgent and effective action to protect the most vulnerable part of the population, such as children and the elderly. In this context, the participatory approach represents a viable option to empower citizens and increase their level of awareness and participation. The involvement of civil society is a potential ally in tackling the still open research challenges. The MAPS-MI 2018-2019 Mapping air pollution in the catchment area of an elementary school of Milan and MAPS-MI 2022-2023 Mobility, environment and participation in the schools of Milan projects are here presented.The main targets of the projects are primary and middle school children, their parents and teachers, with some activities extended to the entire citizenship. Starting from the survey on parents' habits and opinions about mobility and air pollution, to the air quality and personal exposure assessment, and the field-testing and development of an environmental education module, the MAPS-MI approach aims to increase knowledge and awareness about air pollution and to involve stakeholders in experimenting practices towards change. The first results suggest that adopting a participatory approach in the fields of exposure science and environmental epidemiology is a winning choice in terms of quality research, participation and community impact.


Comparison of Locking Plate Fixation and Coracoclavicular Ligament Reconstruction for Neer Type 2B Distal Clavicle Fractures.
There remains no consensus regarding which repair technique provides the most optimal results for unstable distal clavicle fractures. To compare radiologic and clinical outcomes between locking plate fixation and anatomic coracoclavicular (CC) ligament reconstruction for patients with unstable distal clavicle fractures. Cohort study; Level of evidence, 3. The study included 41 patients with Neer type 2B distal clavicle fracture. In group A (n = 15), patients were treated using CC ligament reconstruction with autologous palmaris longus tendon, artificial tape, and Steinmann pin fixation; in group B (n = 26), patients were treated using anatomic locking plate fixation. All patients had a minimum 2 years of follow-up. CC distance and arthrosis of the acromioclavicular joint were assessed radiographically. Clinical outcomes-including range of motion, visual analog scale for pain, American Shoulder and Elbow Surgeons rating scale, and Constant score-were compared between the groups using the paired Student t test and Fisher exact test. Bone union was attained in all patients. In both groups, the CC distance decreased significantly from presurgery to final follow-up: group A, from 16.25 ± 4.75 to 7.66 ± 2.61 mm (P < .001); group B, from 17.3 ± 4.07 to 9.33 ± 2.01 mm (P < .001). The final CC distance was significantly greater in group B (7.66 vs 9.33 mm in groups A and B, respectively; P = .028). Osteoarthritis of the acromioclavicular joint occurred in 13 of 41 patients (3 in group A and 10 in group B). At final follow-up, there was no statistical significance between the groups in range of motion, and clinical outcome scores were satisfactory in both groups, with no statistical difference between them. Anatomic locking plate and anatomic reconstruction of the CC ligament showed good clinical results, so both techniques can be considered reliable for restoring stability. However, CC ligament reconstruction had better CC distance on radiologic assessment and did not require removal surgery, so it may be the preferable surgical option to treat unstable distal clavicle fractures (Neer type 2B).


A comparative cost analysis of digital fundus imaging and direct fundus examination for assessment of diabetic retinopathy.
The objective of this study was to compare the cost between two procedures for fundus examination in patients with diabetes. In our setting, two alternatives for fundus examination are available for patients with diabetes. In the first alternative, a digital image is taken with a nonmydriatic fundus camera when the patient is at the endocrinology consultation, and the image is then examined by an ophthalmologist. In the second alternative, a direct fundus examination is made by an ophthalmologist. We calculated the costs of both procedures from both Public Healthcare System (PHS) and patient perspectives using the official scales to compute personnel, consumables, capital cost of equipment, travel expenses, and time loss of the patient caused by attending the consultation. The first alternative (digital fundus image) required 2.69, 0.03, and 1.62 Euros per patient for personnel, consumables, and capital cost of the equipment, respectively. A direct fundus examination was needed in 31% of patients that had an additional cost of 0.97 Euros per patient for the PHS plus 14.97 Euros per patient because of travel cost and loss of income. The second alternative (direct fundus examination) required 2.69, 0.11, and 0.33 Euros per patient for personnel, consumables, and capital cost, respectively. All patients in this second alternative had to attend a consultation that implied travel and loss of income costs. Attending a consultation represented a cost of 48.29 Euros per patient. From the PHS perspective, direct fundus examination is less costly than using digital fundus images. The higher cost of the digital fundus option is a consequence of the higher capital costs required by the equipment needed to obtain the digital image. However, from a global perspective, the digital image alternative is more convenient because the travel cost and loss of income of the patient are lower.


Pharmacogenetic testing in the clinical management of schizophrenia: a decision-analytic model.
Clinical application of pharmacogenetic testing has been proposed as a means of improving treatment outcomes in psychiatry. The identification of a putative genetic test for better clozapine response in schizophrenia offers an opportunity to evaluate the cost-effectiveness of such testing. The authors performed a cost-effectiveness analysis of a genetic test that may identify individuals with greater likelihood of responding to clozapine treatment. We modeled a target population of schizophrenia patients in an acute psychotic episode, using a lifetime time horizon and societal perspective. Outcome measures included life expectancy, quality-adjusted life expectancy, costs, and incremental cost-effectiveness. Effects of variations in testing parameters were also examined. For a 30-year-old with schizophrenia, applying the pharmacogenetic test and treating those predicted to respond to clozapine with clozapine-first cost US $47,705 per additional quality-adjusted life-year, compared with treating all patients with conventional agents and reserving clozapine for treatment-resistant patients. In 1-way sensitivity analyses, test sensitivity and cost had the greatest impact on the incremental cost-effectiveness. We conclude that pharmacogenetic tests may achieve utility in clinical psychiatry, although their cost-effectiveness depends on several clinical parameters. More consistent reporting of test parameters such as sensitivity and specificity would greatly facilitate assessment of future pharmacogenetic studies.


Effect of blood pressure lowering medications on leg ischemia in peripheral artery disease patients: A meta-analysis of randomised controlled trials.
It has been suggested that anti-hypertensive medications may worsen leg ischemia in peripheral artery disease (PAD) patients. We undertook a meta-analysis to assess the effect of anti-hypertensive medications on measures of leg ischemia including maximum walking distance (MWD), pain free walking distance (PFWD) and ankle brachial pressure index (ABPI). A meta-regression was performed to evaluate whether the effect of the anti-hypertensive medications on mean arterial pressure (MAP) was associated with changes in ABPI, MWD or PFWD. A systematic literature search was performed to identify placebo controlled randomized control trials (RCT) testing anti-hypertensive medications, which reported baseline and follow-up measurements of: MAP and MWD, PFWD or ABPI in patients with intermittent claudication (IC) due to PAD. A meta-analysis was performed on 5 RCTs comprising a total of 180 and 127 patients receiving anti-hypertensive medications and placebo respectively. This analysis suggested that anti-hypertensive medication did not significantly affect MWD, PFWD or ABPI. In contrast, the meta-regression analysis showed that the reduction in MAP due to the anti-hypertensive drugs was positively correlated with increased MWD during follow-up (β = 8.371, p = 0.035). Heterogeneity across studies, as assessed by I2, was high. The follow-up period within the included trials was generally short with 3 out of 5 studies having a follow-up period of ≤ 6 weeks. This study suggests that anti-hypertensive treatment does not worsen but may improve leg ischemia in PAD patients. Larger multicenter trials with longer anti-hypertensive treatment periods are required to clarify the effect of anti-hypertensives on leg ischemia in PAD patients.


Canine ocular protothecosis: A review of 14 cases.
To examine a series of 14 cases of canine ocular protothecosis from archived cases from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW), and compare gross and histologic findings. Archival records from COPLOW were searched for canine cases of ocular protothecosis. Fourteen cases that contained matching criteria were identified, and gross and histologic findings, and clinical records for each case were tabulated, examined, and compared (2001-2013). Of the 14 cases identified, six had evidence of systemic disease, as per clinical history. Two of the 14 cases had Prototheca identified via cytology of ocular fluid or retinal exudate; in the remainder of cases, Prototheca identified via cytology of ocular fluid or retinal exudate in the remaining 12 cases, Prototheca was identified upon histologic examination of the submitted globe(s). Presenting ocular clinical signs were variable and nonspecific. Duration of ocular clinical signs varied from days to months. Fundoscopically, white membranes or plaques were identified on or around the retina in five cases. Retinal detachment was identified in 13 of the 14 submitted globes on gross examination following fixation and sectioning. The predominant histologic finding was granulomatous chorioretinitis with retinal detachment, with variable numbers of Prototheca within the inflammatory infiltrate. Due to the nonspecific nature of the ocular signs, a diagnosis of protothecosis generally is not made until enucleation and histopathologic examination of the globe(s). Retinal detachment and blindness were common. Cytologic sampling of retinal plaques and exudate may provide a rapid way to identify Prototheca.


Expression levels of GSTA2 and APOD genes might be associated with carotenoid coloration in golden pheasant (Chrysolophus pictus) plumage.
Carotenoids, which generate yellow, orange, and red colors, are crucial pigments in avian plumage. Investigations into genes associated with carotenoidbased coloration in avian species are important; however, such research is difficult because carotenoids cannot be synthetized in vertebrates as they are only derived from dietary sources. Here, the golden pheasant (Chrysolophus pictus) was used as a model in analysis of candidate gene expression profiles implicated in carotenoid binding and deposition. Using mass and Raman spectrometry to confirm the presence of carotenoids in golden pheasant feathers, we found C40H54O and C40H56O2 in feathers with yellow to red colors, and in the rachis of iridescent feathers. The global gene expression profiles in golden pheasant skins were analyzed by RNA-seq and all six carotenoid binding candidate genes sequenced were studied by realtime PCR. StAR4, GSTA2, Scarb1, and APOD in feather follicles showed different expressions in red breast and orange nape feathers compared with that of iridescent mantle feathers. Further comparison of golden pheasant yellow rump and Lady Amherst's pheasant (Chrysolophus amherstiae) white nape feathers suggested that GSTA2 and APOD played a potential role in carotenoid-based coloration in golden pheasant.


A health-related fitness and functional performance test battery for middle-aged and older adults: feasibility and health-related content validity.
To evaluate the feasibility and health-related content validity of 6 health-related fitness (HRF) and 3 functional performance (FP) tests among middle-aged and older persons. Cross-sectional methodologic study. Field laboratories in 3 communities of northeast Finland. A regionally representative, community-based cohort of 55- to 79-year-old men (n=501) and women (n=632). Not applicable. Health-related test exclusion rates (%) by age groups and odds ratios (ORs) of subjective health outcomes by fitness categories (least 20%, next 40%, most fit 40%). The health-related test exclusion rates increased with age, mainly because of musculoskeletal health limitations among the women and cardiovascular and musculoskeletal health limitations among the men. With the exception of dynamic back extension, 1-leg squat, 1-leg standing balance, and the 1-km walk among the women 75 years and older, 85% or more of the subjects qualified for the HRF tests and 95% or more for the FP tests. Strong and graded associations were found for cardiorespiratory and musculoskeletal fitness and the FP test levels with perceived health and functional ability status among both the men and the women (OR range, 2-31). The motor fitness test level was primarily associated with functional ability status. All the HRF and FP tests showed health-related content validity, and 4 of 6 of the HRF tests and all of the FP tests proved to be safe, with minor health-related test exclusions for middle-aged and older adults. The findings may help to target physical activity intervention toward persons at high risk for declining health and functional ability.