Oral manifestations of papular-purpuric 'gloves and socks' syndrome due to parvovirus B19 infection: the first case presented in Greece and review of the literature.
Papular-purpuric 'gloves and socks' syndrome (PPGSS) is a novel, rare, self-limited dermatosis initially described in 1990. It is characterized by painful, pruritic edema and erythema, rapidly evolving to papular-purpuric lesions on the distal extremities, in a gloves-and-socks distribution, accompanied by fever and oral lesions such as petechiae, vesiculopustules and small erosions. Parvovirus B19 has been implicated in most cases as the etiological factor. Herein we present the first case of PPGSS in a 42-year-old Greek man with von Willebrand disease. On admission the patient was febrile, and presented acral edema and erythema rapidly followed by purpuric lesions on the same sites, and palatal petechiae. Complete remission of the exanthem occurred 7 days after hospitalization. Clinical and laboratory evaluation including serologic tests and PCR, confirmed the presence of parvovirus B19. Review of the existing literature on this novel syndrome and its association with parvovirus B19 is also presented.


A comparison of antibacterial inhibitory effect on Streptococcus mutans and tensile strength between chitosan-based bonding adhesives and commercial products.
Adhesive bonding is the material used to attach a bracket to the enamel surface of the tooth. Streptococcus mutans contributes to enamel demineralization during orthodontic treatment. To analyze the antimicrobial inhibitory effect of Streptococcus mutans bacteria and tensile strength of chitosan and CaCO3-based adhesive bonding material. The investigation constituted laboratory experimental research featuring analytical observation and a random sampling method. The antibacterial inhibitory effect of chitosan and CaCO3-based adhesive bonding against Streptococcus mutans involved six groups: two control groups using commercial light cure and self-cure adhesive bonding products and four groups using adhesive bonding consisting of 75% CaCO3 + 17.6% Bis-GMA + 22.4% MMA with various percentages of chitosan composition (A1: 25%, A2: 50%, A3: 75%, and A4: 100%) each group consisting of two samples (n = 12). A diametric test was conducted consisting of three samples (n = 15) to measure the tensile strength of each group. Data were analyzed by a combination of one-way analysis of variance and least significant difference tests. The antibacterial inhibitory effect showed significant differences between groups (A1: 2.9467 ± 0.4163, A2: 3.6500 ± 0.6245, A3: 5.1267 ± 0.2517, A4: 4.7267 ± 0.9238; P = 0.0000; P < 0.05). A diametric tensile strength test confirmed significant differences between groups (A1: 7.2733 ± 5.0046, A2: 6.7667 ± 4.4346, A3: 6.4533 ± 2.9994, A4: 1.0058 ± 1.0058, K1: 15.6167 ± 3.1250; P = 0.009; P < 0.05). Chitosan-based adhesive bonding with good tensile strength has an antibacterial inhibitory effect against Streptococcus mutans.


Decreased Regional Cerebral Perfusion at Resting State in Acute Posttraumatic Stress Disorder Resulting From a Single, Prolonged Stress Event.
This study evaluated the altered regional cerebral blood flow (rCBF) in resting state in patients with acute posttraumatic stress disorder (PTSD) 3 months after trauma. The rCBF was measured in 30 patients with acute PTSD and 36 healthy controls. Survivors with acute PTSD showed decreased rCBF, the Clinician-Administered PTSD Scale score correlated negatively with the rCBF, and rCBF at resting state decreased in acute PTSD. PTSD symptom severity was associated with diminished cerebral blood flow in the right insular cortex and right orbital medial frontal gyrus. The rCBF may predict PTSD symptom severity.


The occurrence of gamma-glutamylphenylalanine in the urine of newborn phenylketonurics.
The urine of untreated phenylketonurics in the first weeks of life contains gamma-glutamylphenylalanine (0.07--0.69 mmol/g creatinine, 12 samples) visible on the normal 2-dimensional electrophoreto-chromatogram. This compound is less prominent or absent when urine from older untreated phenylketonurics is examined and is not seen in normal urine.


Molecular characterization and developmental expression patterns of apolipoprotein A-I in Senegalese sole (Solea senegalensis Kaup).
The apolipoprotein A-I (ApoA-I) is an essential component of the high density lipoproteins (HDL). In this study, the cDNA and genomic sequences of this apolipoprotein were characterized for first time in Solea senegalensis. The predicted polypeptide revealed conserved structural features including ten repeats in the lipid-binding domain and some residues involved in cholesterol interaction and binding. The gene structure analysis identified four exons and three introns. Moreover, the synteny analysis revealed that apoA-I did not localize with other apolipoproteins indicating a divergent evolution with respect to the apoA-IV and apoE cluster. The phylogenetic analyses identified two distinct apoA-I paralogs in Ostariophysi (referred to as Ia and Ib) and only one (Ib) in Acanthopterygii. Whole-mount in situ hybridization located the apoA-I signal mainly in the yolk syncytial layer in lecitotrophic larval stages. Later at mouth opening, the mRNA signals were detected mainly in liver and intestine compatible with its role in the HDL formation. Moreover, a clear signal was detected in some regions of the brain, retina and neural cord suggesting a role in local regulation of cholesterol homeostasis. After metamorphosis, apoA-I was also detected in other tissues such as gills, head kidney and spleen suggesting a putative role in immunity. Expression analyses in larvae fed two diets with different triacylglycerol levels indicated that apoA-I mRNA levels were more associated to larval size and development than dietary lipid levels. Finally, qPCR analyses of immature and mature transcripts revealed distinct expression profiles suggesting a posttranscriptional regulatory mechanism.


Pinitol attenuates LPS-induced pneumonia in experimental animals: Possible role via inhibition of the TLR-4 and NF-κB/IκBα signaling cascade pathway.
Pneumonia is a chronic disorder of the respiratory system associated with worsening quality of life and a significant economic burden. Pinitol, a plant cyclic polyol, has been documented for immune-inflammatory potential. The aim of present investigation was to evaluate the potential and possible mechanism of action of pinitol against lipopolysaccharide (LPS)-induced pneumonia in the experimental animal model. Pneumonia was induced in Sprague-Dawley rats by intratracheal administration of LPS (2 mg/kg). Animals were treated with either vehicle or dexamethasone or pinitol (5 or 10 or 20 mg/kg). Potential of pinitol against LPS-induced pulmonary insult was assessed based on behavioral, biochemical, molecular, and ultrastructural studies. Intratracheal instillation of LPS induced significant (P < .05) inflammatory infiltration in bronchoalveolar lavage fluid (BALF) and lung tissue reflected by elevated pleural effusion volume, lung edema, BALF polymorphonuclear leukocytes count and lung myeloperoxidase levels, which was attenuated by pinitol (10 and 20 mg/kg) administration. Pinitol also markedly (P < .05) inhibited LPS-induced alterations in electrocardiographic, hemodynamic changes, right ventricular, and lung function tests. The LPS-induced downregulated nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1), whereas upregulated transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), and inducible nitric oxide synthase (iNOs) lung messenger RNA expressions were significantly (P < .05) inhibited by pinitol. Western blot analysis suggested pinitol markedly (P < .05) decreased nuclear factor-κB (NF-κB), inhibitor of nuclear factor κB (IkBα), toll-like receptor 4 (TLR-4), and cyclooxygenase-II (COX-II) protein expressions in the lung. These findings were further supported by histological and ultrastructural analyses of lung tissue that show pinitol significantly (P < .05) ameliorates LPS-induced aberrations in lung tissue. In conclusion, pinitol attenuated LPS-induced pneumonia via inhibition of TLR-4 to downregulate the NF-κB/IκBα signaling cascade and thus ameliorated the production of proinflammatory cytokines (TNF-α, ILs, NLRP3, and TGF-β), inflammatory mediators (COX-II and iNOs) and elevated oxidative stress (Nrf-2 and HO-1).


Vacuolin-1 enhances RA-induced differentiation of human myeloblastic leukemia cells: evidence for involvement of a CD11b/FAK/LYN/SLP-76 axis subject to endosomal regulation that drives late differentiation steps.
Retinoic acid(RA), an embryonic morphogen, regulates cell differentiation. Endocytosis regulates receptor signaling that governs such RA-directed cellular processes. Vacuolin-1 is a small molecule that disrupts endocytosis, motivating interest in its effect on RA-induced differentiation/arrest. In HL-60 myeloblastic-leukemia cells, RA causes differentiation evidenced by a progression of cell-surface and functional markers, CD38, CD11b, and finally reactive oxygen species(ROS) production and G1/0 cell cycle arrest in mature cells. We found that Vacuolin-1 enhanced RA-induced CD11b, ROS and G1/0 arrest, albeit not CD38. Enhanced CD11b expression was associated with enhanced activation of Focal Adhesion Kinase(FAK). Adding vacuolin-1 enhanced RA-induced tyrosine phosphorylation of FAK, Src Family Kinases(SFKs), and the adaptor protein, SLP-76, expression of which is known to drive RA-induced differentiation. Depleting CD11b cripples late stages of progressive myeloid differentiation, namely G1/0 arrest and inducible ROS production, but not expression of CD38. Loss of NUMB, a protein that supports early endosome maturation, affected RA-induced ROS and G1/0 arrest, but not CD38 expression. Hence there appears to be a novel CD11b/FAK/LYN/SLP-76 axis subject to endosome regulation which contributes to later stages of RA-induced differentiation. The effects of vacuolin-1 thus suggest a model where RA-induced differentiation consists of progressive stages driven by expression of sequentially-induced receptors.


The significant effect of HLA-DRB1 matching on long-term kidney graft outcome.
Serotyping and genotyping (polymerase chain reaction with sequence-specific oligonucleotide probes method) were conducted on 520 unrelated individuals to determine the linkage disequilibrium of HLA-B and HLA-DRB1. Analyses of 511 kidney transplants (300 related and 211 cadaver recipients) were carried out at 4 transplant centers using the linkage disequilibrium of HLA-B and HLA-DRB1 established previously. All transplant recipients received CsA immunosuppression and were transplanted from June 1983 to December 1991. There were 51 significant linkages formed between HLA-B and HLA-DRB1 alleles (P < 0.05). DRB1-compatible transplants experienced a comparable 5-year graft success rate of 94% as did the HLA-identical recipients with a 100% 5-year success rate. However DRB1-incompatible recipients displayed a significantly reduced 5-year graft survival rate of 73% (73% vs. 94% P < 0.01). The 5-year graft survival rate of HLA-DR-incompatible recipients of 71% was compatible to the 73% for HLA-DRB1-incompatible recipients. No variation of rejection rate for DRB1-compatible grafts was seen in any of the 4 transplant centers. The results also indicated that HLA-DRB1 compatibility was essential for optimal success rate, regardless of HLA class I mismatches. The overall conclusion was that matching for HLA-DR was important to achieve optimal kidney graft survival on the molecular level but not on the serotyping level.


Diagnostic value of serum IGF-I and IGFBP-3 in growth hormone disorders in adults.
To investigate the diagnostic value of serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) measurements in adult patients with acromegaly and GH deficiency (GHD). Serum IGF-I and IGFBP-3 levels were measured in 39 active acromegalic patients, 34 adult patients with GHD and 150 healthy adults. Disease activity in patients with acromegaly was confirmed by nadir GH levels during an oral glucose tolerance test (OGTT). Among patients with acromegaly, 15 had not been treated previously and 24 had been treated but not cured. GHD in adults was diagnosed by an insulin tolerance test (ITT). Among patients with GHD, 15 were aged 20-40 years (9 men and 6 women) and 19 were aged over 40 years (9 men and 10 women). One hundred and fifty healthy subjects were recruited as a control group. To compare the individual serum IGF-I and IGFBP-3 levels of patients with the results of the gold standard, we calculated age- and sex-corrected standard deviation scores (SDS) for individual IGF-I and IGFBP-3 levels. The sensitivities of serum IGF-I and IGFBP-3 measurements for the disease diagnosis were analyzed using the mean +/- 2 SD of the values of healthy control subjects as a diagnostic cutoff, defining 95% specificity. The mean IGF-I and IGFBP-3 SDS levels were significantly higher in active acromegalic patients, both untreated and treated but not cured, than in the control subjects (p < 0.05). The sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of acromegaly were 97.4 and 81.8%, respectively. In untreated patients with acromegaly, the sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of disease were 100 and 100%, while these were 95.8 and 72.7% in treated patients with acromegaly. In adult patients with GHD, the mean IGF-I and IGFBP-3 SDS were significantly lower than those of the control subjects (IGF-I, -2.2 +/- 0.8 vs. 0.0 +/- 1.0 SDS, p < 0.0001); IGFBP-3, -1.7 +/- 1.2 vs. 0.0 +/- 1.0 SDS, p < 0.0001), but there was a considerable overlap between GHD in adults and the controls. In all patients with GHD, the sensitivities of serum IGF-I and IGFBP-3 measurements were 64.7 and 52.9%, respectively. In the group of women aged 20-40 years, the sensitivity of IGF-I measurement for the diagnosis of GHD was 100%, although the number of patients was only 6. Both serum IGF-I and IGFBP-3 measurements are comparable to an oral glucose tolerance test in patients with untreated acromegaly, but in acromegalic patients that have undergone surgery and/or radiotherapy, serum IGF-I is more valuable for determining disease activity than serum IGFBP-3. Serum IGF-I and IGFBP-3 measurements are not valuable for the diagnosis of GHD in adults, but in women aged 20-40 years serum IGF-I measurement appears to be useful in the diagnosis of GHD.


Factors associated with benefit finding and mental health of patients with cancer: a systematic review.
This systematic review was performed to identify the association between benefit finding (BF) and anxiety, depression, and distress, as well as to find factors related to BF in adult cancer patients. Five English databases and four Chinese databases were searched to identify eligible articles about BF in adult cancer patients from inception to 4 July 2021. Literature screening, data extraction, and quality assessment were carried out by two reviewers independently according to the inclusion and exclusion criteria. Qualitative synthesis was used to summarize the results. Twenty-one studies involving 9601 cancer patients were included in this study. Qualitative analysis showed that BF was negatively related to anxiety, depression, and distress. Factors associated with BF included sociodemographic factors, disease-related factors, and psychological and environmental factors. Healthcare providers should pay attention to the summarized factors of BF and construct intervention programs based on the controllable factors to improve BF in adult cancer patients, thus promoting the recovery of patients.


Primary transitional cell carcinoma of the endometrium: Exceptional presentation of a rare tumor.
Transitional cell carcinoma (TCC) is an extremely rare gynecologic tumor, particularly in the endometrium. All endometrial TCC cases reported so far in the literature were diagnosed at relatively advanced stages. In the present article, we report a pure primary endometrial TCC initially revealed by an abdominal mass and classified as an International Federation of Gynecology and Obstetrics stage IA. The patient was successfully treated with surgery and adjuvant radiotherapy. This case highlights the importance of early diagnosis of gynecologic malignancies, offering satisfactory outcomes even in the rarest types for which evidence-based recommendations are lacking.


Identification of The Unique Subtype of Macrophages in Aneurysm Lesions at the Growth Phase.
Recent experimental studies have defined intracranial aneurysms as a macrophage-mediated chronic inflammatory disease affecting intracranial arteries. Although there are various subtypes in macrophages, what type of macrophages is present in lesions during the disease development remains to be elucidated. The previously-established aneurysm model of rats was used. Macrophages were labeled with the fluorescent protein and isolated by a laser-microdissection method. The comprehensive gene expression profile analyses and gene ontology analyses was then done to identify a macrophage subtype present in lesions at the growth phase. The gene expression profile data of total 52 macrophages infiltrating into the lesions was acquired. The principal component analysis revealed the monotonous macrophage subtype. By comparing the profile identified with one from in vitro-differentiated M0 or M1 macrophages, the macrophages in the lesions were belonged to the simple and unique subtype. Because the perception of signaling from nervous system was highlighted as up-represented terms through gene ontology analyses, the macrophage subtype in lesions at the growth phase might be differentiated under the influence of nervous system in the microenvironment. The histopathological examinations supported the above notion by confirming the presence of nerves in the adventitia. The findings from the present study have provided the useful insights about the macrophage subtype in aneurysm lesions at the growth phase and also proposed its ability as a therapeutic target.


Syntheses and structural studies of Schiff bases involving hydrogen bonds.
New Schiff bases have been prepared by reacting 3-hydroxy-4-pyridine- carboxaldehyde with various amines. NMR spectroscopic methods provided clear evidence that the Schiff bases exist in the solid state and in solution as hydroxyimino tautomers with the E-configuration. A study of the stabilities of the tautomeric forms and the different conformers has been carried out using density functional calculations at the B3LYP/6-31G** level.


Two New Phenolic Constituents from the Stems of Euphorbia griffithii.
Phytochemical studies on MeOH extract of stems of Euphorbia griffithii led to the isolation of one new hydrolyzable tannin dimer, corilagiffithiin (1) and one new galloyl-glucoside (2), alongside six known ones (3-8). Their structures and absolute configurations were determined by in depth spectroscopic analyses and comparison of their 1D NMR and MS data with literature reported values. Configurations of sugar moieties were determined by acidic hydrolysis and subsequent GC analysis of their corresponding trimethylsilylated L-cysteine adduct. At a concentration of 50 μM, compounds 1-3 showed no anti-inflammatory activities.


Data collected to assess the effect of inquiry-based learning on environmental knowledge and attitudes among pre-service biology teachers in Tanzania.
The proliferation of global environmental problems has necessitated the need to re-examine the environmental impacts caused by human-nature relations. Yet individual attitudes and environmental literacy remain among the critical determinants of environmental sustainability. Consequently, environmental psychology has been one of the most effective tools for shaping people's actions in favor of the environment. As such, this article presents a dataset that describes an intervention carried out to explore the effect of inquiry-based learning on shaping environmental attitudes (EAs) and knowledge of pre-service biology teachers in selected teacher colleges (TCs) in Tanzania. Data were collected from four TCs located in four different regions of Tanzania (N = 333). Particularly, EAs were measured using the two-factor model of ecological attitudes (2-MEV) by assessing two uncorrelated domains of environmental attitudes: Preservation and Utilization of nature. In addition, a Competence Model for Environmental Education was used to measure the three dimensions (system knowledge, action-related knowledge, and effectiveness knowledge) of environmental knowledge among pre-service biology teachers. A modified design of the Solomon four-group was employed to guide the intervention in measuring the level of change in EAs and environmental knowledge before and after the study intervention. A paired-sample t-test was used to assess the effect of the intervention on TCs that had pre- and post-tests, given the variation in the number of subjects in each TC. In addition, the one-way analysis of variance (ANOVA) compared the mean scores of the combined study groups at the post-test. Besides, in the regression analysis, Hayes' PROCESS macro (version 4.1) was used to assess the moderation effect of the Social Desirability Responding (SDR) on the relationships between EAs and environmental knowledge. Likewise, age (in years) was entered as a covariate in the regression model of the Statistical Product and Service Solution (IBM SPSS version 25). The presented dataset can act as a basis for improving the status of environmental education delivery in teacher education in Tanzania and other areas with similar or related contexts. Thus, program-specific interventions could be designed for prospective biology teachers as potential change agents in shaping how people interact with the environment.


Associations between infant feeding and the size, tempo and velocity of infant weight gain: SITAR analysis of the Gemini twin birth cohort.
Infant growth trajectories, in terms of size, tempo and velocity, may programme lifelong obesity risk. Timing of breastfeeding cessation and weaning are both implicated in rapid infant growth; we examined the association of both simultaneously with a range of growth parameters. Longitudinal population-based twin birth cohort. The Gemini cohort provided data on 4680 UK infants with a median of 10 (interquartile range=8-15) weight measurements between birth and a median of 6.5 months. Age at breastfeeding cessation and weaning were reported by parents at mean age 8.2 months (s.d.=2.2, range=4-20). Growth trajectories were modelled using SuperImposition by Translation And Rotation (SITAR) to generate three descriptors of individual growth relative to the average trajectory: size (grams), tempo (weeks, indicating the timing of the peak growth rate) and velocity (% difference from average, reflecting mean growth rate). Complex-samples general linear models adjusting for family clustering and confounders examined associations between infant feeding and SITAR parameters. Longer breastfeeding (>4 months vs never) was independently associated with lower growth velocity by 6.8% (s.e.=1.3%) and delayed growth tempo by 1.0 (s.e.=0.2 weeks), but not with smaller size. Later weaning (⩾6 months vs <4 months) was independently associated with lower growth velocity by 4.9% (s.e.=1.1%) and smaller size by 102 g (s.e.=25 g). Infants breastfed for longer grew slower for longer after birth (later peak growth rate) but were no different in size, while infants weaned later grew slower overall and were smaller but the timing of peak growth did not differ. Slower trajectories with a delayed peak in growth may have beneficial implications for programming later obesity risk. Replication in cohorts with longer follow-up, alternative confounding structures or randomised controlled trials are required to confirm the long-term effects and directionality, and to rule out residual confounding.


Biofilm retention by 3 methods of ligation on orthodontic brackets: a microbiologic and optical coherence tomography analysis.
The aim of this study was to evaluate biofilm retention around orthodontic brackets related to the method of ligation by using optical coherence tomography (OCT) and microbiologic sampling. Seventy-five plastic central incisors for dentures were divided into 3 groups and used with metal brackets with a 0.022-in slot with elastomeric ligature (n = 25), metal brackets with a 0.022-in slot with steel wire ligature (n = 25), and self-ligating brackets with a 0.022-in slot (n = 25). The samples were submersed in a suspension of Streptococcus mutans, genetically engineered to express green fluorescent protein, at 37°C for 72 hours to allow biofilm formation. The samples were then submitted to microbiologic analysis and OCT imaging. The microbiologic analysis and the OCT showed significant differences in biofilm formation depending on the ligating method. Brackets ligated with elastomeric rings held more S mutans biofilm, and steel wire ligation had less biofilm retention compared with the other brackets. This study provided validation that OCT can be used as a potential qualitative marker of total plaque bacteria that can be rapidly and reliably visualized around orthodontic brackets.


Tree aboveground carbon storage correlates with environmental gradients and functional diversity in a tropical forest.
Tropical forests play a disproportionately important role in the global carbon (C) cycle, but it remains unclear how local environments and functional diversity regulate tree aboveground C storage. We examined how three components (environments, functional dominance and diversity) affected C storage in Dinghushan 20-ha plot in China. There was large fine-scale variation in C storage. The three components significantly contributed to regulate C storage, but dominance and diversity of traits were associated with C storage in different directions. Structural equation models (SEMs) of dominance and diversity explained 34% and 32% of variation in C storage. Environments explained 26-44% of variation in dominance and diversity. Similar proportions of variation in C storage were explained by dominance and diversity in regression models, they were improved after adding environments. Diversity of maximum diameter was the best predictor of C storage. Complementarity and selection effects contributed to C storage simultaneously, and had similar importance. The SEMs disengaged the complex relationships among the three components and C storage, and established a framework to show the direct and indirect effects (via dominance and diversity) of local environments on C storage. We concluded that local environments are important for regulating functional diversity and C storage.


A refugee's perspective on their neurosurgical care in North America.
There is a growing population of refugees within North America and an increasing awareness of their unique medical requirements. These requirements include both a well-recognized need to understand the different pathologies that can present in these patients as well as the rarely described need to understand their unique perspective and how this can impact their medical care, especially for routine neurosurgical conditions. This paper highlights a refugee's perspective toward the medical system in North America and documents how several aspects of this unique perspective hindered or delayed the care for the management of this patient with a cervical cord tumor. A 34-year-old female Somalian refugee presented with an ependymoma to Vancouver General Hospital 3 days after arriving in North America. The tumor was removed through a standard posterior cervical laminectomy approach. The patient and her care workers were interviewed 6 months postoperatively to determine if any aspects of care were negatively impacted by her refugee status. Problems related to communication, medical history, mistrust of care workers, familial support, and access to follow-up care were recognized and recommendations for improvements provided. It is well known that the North American physicians must be familiar with the unique spectrum of medical conditions within the refugee community. This paper highlights that physicians must also be aware that refugees may have a unique perspective on our health care system that can negatively influence their care for even routine neurosurgical conditions.


DYW domain structures imply an unusual regulation principle in plant organellar RNA editing catalysis.
RNA editosomes selectively deaminate cytidines to uridines in plant organellar transcripts-mostly to restore protein functionality and consequently facilitate mitochondrial and chloroplast function. The RNA editosomal pentatricopeptide repeat proteins serve target RNA recognition, whereas the intensively studied DYW domain elicits catalysis. Here we present structures and functional data of a DYW domain in an inactive ground state and activated. DYW domains harbour a cytidine deaminase fold and a C-terminal DYW motif, with catalytic and structural zinc atoms, respectively. A conserved gating domain within the deaminase fold regulates the active site sterically and mechanistically in a process that we termed gated zinc shutter. Based on the structures, an autoinhibited ground state and its activation are cross-validated by RNA editing assays and differential scanning fluorimetry. We anticipate that, in vivo, the framework of an active plant RNA editosome triggers the release of DYW autoinhibition to ensure a controlled and coordinated cytidine deamination playing a key role in mitochondrial and chloroplast homeostasis.


Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing.
Metformin is a well-known anti-diabetic drug that has been repurposed for several emerging applications, including as an anti-cancer agent. It boasts the distinct advantages of an excellent safety and tolerability profile and high cost-effectiveness at less than one US dollar per daily dose. Epidemiological evidence reveals that metformin reduces the risk of cancer and decreases cancer-related mortality in patients with diabetes; however, the exact mechanisms are not well understood. Energy metabolism may be central to the mechanism of action. Based on altering whole-body energy metabolism or cellular state, metformin's modes of action can be divided into two broad, non-mutually exclusive categories: "direct effects", which induce a direct effect on cancer cells, independent of blood glucose and insulin levels, and "indirect effects" that arise from systemic metabolic changes depending on blood glucose and insulin levels. In this review, we summarize an updated account of the current knowledge on metformin antitumor action, elaborate on the underlying mechanisms in terms of the hallmarks of cancer, and propose potential applications for repurposing metformin for cancer therapeutics.


Role of Helicobacter pylori eradication in patients with functional dyspepsia.
Helicobacter pylori (H. pylori) is implicated in the pathogenesis of functional dyspepsia (FD). There is conflicting data regarding the benefit of H. pylori eradication for symptom relief in FD. To study the benefit of eradicating H. pylori in patients with FD as compared to standard medical treatment (SMT). Secondary aims were to find efficacy of H. pylori eradication therapy, recurrence of H. pylori after eradication, and predictors of efficacy. Consecutive adult patients of FD (ROME IV) with H. pylori infection presenting in the outpatient department of our hospital were enrolled. Patients with Global Overall Symptom (GOS) scale > 2 and H. pylori infection were included. Patients were randomized into two groups: group 1 received H. pylori eradication therapy and group 2 received SMT. Treatment success was defined as symptom relief (GOS score < 2 and reduction by at least 2 points at 6 months) and H. pylori eradication was defined as stool antigen negative at 4 weeks. Of 329 participants with FD, 253 were H. pylori positive (rapid urease test and stool antigen test) (76.89%). After exclusions, 202 were randomized into two groups of 101 each. Thirty-two patients in group 1 and 31 in group 2 had treatment success (31.7% vs. 30.7%, p=1.000). The efficacy of H. pylori eradication therapy was 74.46% (70/94). H. pylori reinfection rate was 26.02% (19/73). H. pylori eradication therapy does not provide additional benefit in symptom relief in patients with FD as compared with SMT. NCT04697641 (retrospectively registered on www.clinicaltrials.gov in January 2021).


Leber's hereditary optic neuropathy associated with multiple sclerosis: Harding's syndrome.
We describe a 32-year-old woman with sequential, severe, painless visual loss in one eye and then the other, and three temporally distinct episodes of neurological disturbance suggestive of demyelination in the spinal cord. She was positive for the T14484C mutation in the mitochondrial genome, one of three common mutations causing Leber's hereditary optic neuropathy. In addition, MRI identified areas of demyelination within the periventricular white matter of the brain and within the spinal cord. The coexistence of multiple sclerosis and Leber's hereditary optic neuropathy (Harding's syndrome) is known to occur more often than would be expected by chance; therefore, screening for the Leber's mutations in multiple sclerosis patients with severe visual loss should be considered because this has important prognostic and genetic implications.


Effect of fatigue on force sensation.
Recent experiments have suggested that a sense of effort can be separated from a sense of developed force or tension in muscular contractions. The evidence for this distinction was examined during submaximal fatiguing contractions. Subjects were required to maintain until maximal endurance a constant isometric force with their right, reference arm, and at 15-s intervals they estimated the magnitude of this force with a matching contraction of the contralateral arm. The matching force produced by the unfatigued limb was the measure of force sensation. Both force and the brachial biceps and triceps EMG were recorded from each arm. During the fatiguing contractions the matching force increased linearly as did the biceps EMG of the fatiguing muscle. The rate of increase was dependent on the level of force exerted. A linear relation between the reference arm EMG and the perceived force was observed, which suggested that the over-estimation of force was due to the increase in the excitatory input to the fatiguing muscle. These results provide support for a centrally mediated theory of force perception, and indicate that during fatigue subjects are unable to estimate accurately the force of contraction. Furthermore, they suggest that under those conditions a sense of tension is not distinguishable from a sense of effort.


A man in his seventies with fatigue and renal failure.
A man in his seventies underwent routine heart examinations as part of workup for kidney transplantation. Unexpected findings led to more extensive investigations and revealed two rare systemic diseases as causes of his heart failure.


Effect of dexamethasone on the growth and differentiation of osteoblast-like cells derived from the human alveolar bone.
This study aimed to investigate the effect of dexamethasone on the growth and differentiation of osteoblast-like cells derived from the human alveolar bone. Bone particles were collected from patients during implant-site preparation. The samples were cultured in a growth medium, and the cells that propagated after two-three weeks were cultured in three types of culture media: group 1, normal medium; group 2, osteogenic medium without dexamethasone; and group 3, osteogenic medium with dexamethasone-for zero, four, seven, and 20 days. DNA and alkaline phosphatase (ALP) measurements and alizarin red/toluidine blue staining were performed. DNA levels were significantly higher in group 2 than in group 1 on day 7 (p < 0.001) and in group 3 on days 4, 7, and 20 (p < 0.041, p < 0.006, and p < 0.001, respectively). Further, total ALP levels were significantly higher in group 3 than in groups 1 on day 20 (p < 0.023). A greater amount of matrix mineralisation was observed in group 3 than in groups 1 and 2. Human alveolar bone cells exhibit improved osteogenic efficacy in terms of osteogenic differentiation when cultured in the presence of dexamethasone. The cell number (total DNA content) decreased in the presence of dexamethasone; however, an increased differentiation of osteoblast-like cells was observed.


Protective Effects of Salvianolate on Myocardial Injury or Myocardial Infarction after Elective Percutaneous Coronary Intervention in NSTE-ACS Patients: A Randomized Placebo-Controlled Trial.
To evaluate the protective effects of salvianolate on percutaneous coronary intervention (PCI) related myocardial injury or myocardial infarction after elective PCI in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients. A total of 149 patients with NSTE-ACS who underwent elective PCI were enrolled. The patients were randomly allocated in a 1:1 ratio to the salvianolate group (74 cases) or the control group (75 cases). After exclusion criteria of coronary angiography, 60 patients with PCI therapy remained in the salvianolate group and 68 in the control group. The incidence and the severity of PCI related myocardial injury or myocardial infarction, in addition to major adverse cardiac events (MACEs) during 1 year follow-up after PCI were studied between the two groups. Multivariate logistic regression analysis was used to determine the independent factors for PCI related myocardial injury or myocardial infarction after elective PCI. Compared with the control group, salvianolate treatment reduced the incidence of PCI related severe myocardial injury or myocardial infarction (11.7% vs. 26.5%, P=0.035). The rate of MACEs or all-cause death within 1 month or 1 year after the procedure was not significantly different between the two groups. Periprocedural treatment with salvianolate reduces the incidence of PCI related severe myocardial injury or myocardial infarction, although it does not influence clinical prognosis. [Chinese clinical trial registry: ChiCTR1800016992].


Structure of the HERG K+ channel S5P extracellular linker: role of an amphipathic alpha-helix in C-type inactivation.
The HERG K+ channel has very unusual kinetic behavior that includes slow activation but rapid inactivation. These features are critical for normal cardiac repolarization as well as in preventing lethal ventricular arrhythmias. Mutagenesis studies have shown that the extracellular peptide linker joining the fifth transmembrane domain to the pore helix is critical for rapid inactivation of the HERG K+ channel. This peptide linker is also considerably longer in HERG K+ channels, 40 amino acids, than in most other voltage-gated K+ channels. In this study we show that a synthetic 42-residue peptide corresponding to this linker region of the HERG K+ channel does not have defined structural elements in aqueous solution; however, it displays two well defined helical regions when in the presence of SDS micelles. The helices correspond to Trp585-Ile593 and Gly604-Tyr611 of the channel. The Trp585-Ile593 helix has distinct hydrophilic and hydrophobic surfaces. The Gly604-Tyr611 helix corresponds to an N-terminal extension of the pore helix. Electrophysiological studies of HERG currents following application of exogenous S5P peptides show that the amphipathic helix in the S5P linker interacts with the pore region of the channel in a voltage-dependent manner.


The analysis of the glaucoma screening event results obtained during the World Glaucoma Week in Zagreb, Croatia.
To report the prevalence of undiagnosed glaucoma, as well as demographic characteristics and risk factors among glaucoma suspects who were detected in a publicly promoted intraocular pressure (IOP) based glaucoma screening event. A total of 2468 subjects older than 18 years participated in the glaucoma screening event in Zagreb, in 2014, which included a medical interview and IOP measurement using Icare tonometer. 256 subjects (10.37%) were identified as glaucoma suspects, out of which 125 (5.06%) subjects underwent further detailed ophthalmic examination and were classified into five diagnostic groups. The prevalence of all types of newly diagnosed glaucoma was 1.175%, while the prevalence of ocular hypertension (OH), primary open-angle glaucoma (POAG), primary angle closure (PAC) and secondary glaucoma (SG) was 0.16%, 0.89%, 0.16% and 0.12%, respectively. The prevalence of newly diagnosed glaucoma in glaucoma suspects was 23.2%. 17.60% of glaucoma suspects were diagnosed as POAG. Older age was statistically significantly associated with POAG (p = 0.001) and PAC (p = 0.029). At the univariate level, refractive errors were a statistically significant predictor of POAG, and those with hyperopia had more than three times larger odds for POAG. At the multivariate level, none of the predictors reached statistical significance. Successful cooperation between healthcare institutions and media can be a useful way of increasing awareness and detection of individuals at an increased risk for developing glaucoma.


The etiology of medical gridlock: causes of emergency department overcrowding in New York City.
Overcrowding of emergency departments in New York City is the most apparent symptom of a crumbling health care system. There is a growing need for the care of a largely impoverished population suffering from an increasing prevalence of AIDS, substance abuse, and psychiatric disease. Institutions crippled by critical shortages of inpatient beds and nurses lack the resources to meet this rising demand. Although the epidemic of medical gridlock began in New York City, it is spreading rapidly to involve other areas of the country. Short-term efforts to resolve this crisis have thus far been unsuccessful. Long-range solutions are likely to be costly and may require a reconfiguration of societal health care priorities.


Assessment of knowledge and attitudes regarding organ donation among doctors and students of a tertiary care hospital.
Organ donation is a lifesaving treatment option for patients with end-organ damage. However, many patients are unable to avail this option due to the low availability of viable organs for transplantation. The availability of donor organs can be improved by increasing awareness and resolving organ donation misconceptions among the general population. It can be assumed that healthcare workers are most aware of the value of organ donation. They are also in a position to influence the willingness of the general population to donate organs after death or sign up for an organ donor card. The knowledge and attitudes of current and future healthcare professionals regarding this subject have neither been evaluated nor considered a topic of priority in the existing Indian medical education program. To evaluate the knowledge, attitudes, and beliefs of licensed medical doctors and undergraduate Bachelor of Medicine and Bachelor of Surgery (MBBS) students and analyze differences between the two groups with respect to the above. A total of 650 doctors and MBBS students from a Tertiary care hospital were included in the study and subjected to a questionnaire with 11 questions. Responses to the questionnaire were analyzed to evaluate knowledge and attitudes regarding organ donation. Statistical analysis was carried out using IBM SPSS Statistics for Windows, version 24. About 29.9% of doctors and 49.8% of students knew about the law governing organ donation. The concept of brain death was entirely understood by only 31.7% of doctors and 14.7% of students. Only 16% of doctors and 3.2% of students had filled an organ donor card. About 40.9% of doctors and 51% of students favored the opt-out system, as followed by western nations. Fear of illegal selling or purchase of organs was predominant in 61.9% of doctors and 52.2% of students. The current study reveals that the medical fraternity's knowledge and personal responsibility need improvements. However, the system also needs to be improved to win their trust.


STEM beam channeling in BaSnO3/LaAlO3 perovskite bilayers and visualization of 2D misfit dislocation network.
A study of the STEM probe channeling in a heterostructured crystalline bilayer specimens is presented here with a goal to guide STEM-based characterization of multilayer structures. STEM analysis of perovskite BaSnO3/LaAlO3 bilayers is performed and the dominating effects of beam channeling on HAADF- and LAADF-STEM are illustrated. To study the electron beam channeling through BaSnO3/LaAlO3 bilayers, probe intensity depth profiles are calculated, and the effects of probe defocus and atomic column alignment are discussed. Characteristics of the beam channeling are correlated to resulting ADF-STEM images, which is then tested by comparing focal series of plan-view HAADF-STEM images to those recorded experimentally. Additionally, discussions on how to visualize the misfit dislocation network at the BaSnO3/LaAlO3 interface using HAADF- and LAADF-STEM images are provided.


Spray-dried multidrug particles for pulmonary co-delivery of antibiotics with N-acetylcysteine and curcumin-loaded PLGA-nanoparticles.
Nowadays, the resistance of bacterial biofilms towards the available antibiotics is a severe problem. Therefore, many efforts were devoted to develop new formulations using nanotechnology. We have developed an inhalable microparticle formulation using spray-drying combining multiple drugs: an antibiotic (tobramycin, ciprofloxacin or azithromycin), N-acetylcysteine (NAC), and curcumin (Cur). The use of PLGA nanoparticles (NP) also allowed incorporating curcumin to facilitate spray drying and modify the release of some compounds. The aerosolizable microparticles formulations were characterized in terms of size, morphology, and aerodynamic properties. Biocompatibility when tested on macrophage-like cells was acceptable after 20 h exposure for concentrations up to at least 32 µg/mL. Antibacterial activity of free drugs versus drugs in the multiple drug formulations was evaluated on P. aeruginosa in the same range. When co-delivered the efficacy of tobramycin was enhanced compared to the free drug for the 1 µg/mL concentration. The combinations of azithromycin and ciprofloxacin with NAC and Cur did not show an improved antibacterial activity. Bacteria-triggered cytokine release was not inhibited by free antibiotics, except for TNF-α. In contrast, the application of NAC and the addition of curcumin-loaded PLGA NPs showed a higher potential to inhibit TNF-α, IL-8, and IL-1β release. Overall, the approach described here allows simultaneous delivery of antibacterial, mucolytic, and anti-inflammatory compounds in a single inhalable formulation and may therefore pave the way for a more efficient therapy of pulmonary infections.


A clinical internship model for the nurse practitioner programme.
Nurse practitioners in Victoria, Australia must be prepared to Masters level before seeking nurse practitioner (NP) endorsement. The challenge from a university curriculum development perspective was to develop a programme that prepares the NP theoretically and clinically for their advanced practice role. The aim of this discussion paper is to outline how the internship model was developed and report the students' opinions on the model. The NP students complete the internship with a suitably qualified mentor which requires them to work together to develop and maintain a clinical learning plan, keep a log of the weekly meetings that shows how the objectives have been achieved. The internship includes advanced clinical assessment, prescribing, diagnostic and treatment skills and knowledge related to the nurse's specialty. The clinical assessment tool incorporates the National Competency Standards for the Nurse Practitioner and allows students and mentors to identify the level of practice and set clinical objectives. Students were asked to give feedback on the clinical internship and overall their comments were favourable, reporting benefits of a clinical mentor in their work and the clinical case presentations. The clinical internship allows the acquisition of knowledge and clinical skills in the clinical specialty with an expert clinical mentor in this innovative programme.


Boosting the electro-oxidation of 5-hydroxymethyl-furfural on a Co-CoS x heterojunction by intensified spin polarization.
The conversion of biomass-derived platform molecules (e.g., 5-hydroxymethyl furfural (HMF)) represents a sustainable route to produce value-added chemicals. Here we report the fabrication of an N-doped carbon nanotube assembled yolk-shell polyhedron with embedded Co-CoS x nanoparticles (NPs) (Y-Co-CoS x @CN) for efficient HMF electrooxidation. DFT calculations demonstrate that the formation of the heterojunction could intensify spin polarization in Co-CoS2, thus achieving effective d-p coupling between the catalyst and reactant/intermediate. As expected, Y-Co-CoS x @CN exhibits excellent HMF electro-oxidation activity at a low applied potential of 1.29 V vs. RHE at 10 mA cm-2 in 0.1 M KOH with 5 mM HMF, affording an FDCA yield of 96% and FE of 93.5%. This work not only sheds light on the catalytic nature of the heterojunction and the underlying mechanisms for the enhancement of HMF electro-oxidation activity, but would also provide a descriptor for the rational design of advanced electro-catalysts.


Functional display of an alpha2 integrin-specific motif (RKK) on the surface of baculovirus particles.
The use of baculovirus vectors shows promise as a tool for gene delivery into mammalian cells. These insect viruses have been shown to transduce a variety of mammalian cell lines, and gene transfer has also been demonstrated in vivo. In this study, we generated two recombinant baculovirus vectors displaying an integrin-specific motif, RKK, as a part of two different loops of the green fluorescent protein (GFP) fused with the major envelope protein gp64 of Autographa californica M nucleopolyhedrovirus. By enzyme linked immunosorbent assays, these viruses were shown to bind a peptide representing the receptor binding site of an alpha2 integrin, the alpha2I-domain. However, the interaction was not strong enough to overcome binding of wild type gp64 to the unknown cellular receptor(s) on the surface of alpha2 integrin-expressing cells (CHO-alpha2beta1) or enhance the viral uptake. After treatment of these cells with phospholipase C, internalization of all viruses was blocked or decreased significantly. However, one of the RKK displaying viruses, AcGFP(K)gp64, was still able to internalize into CHO-alpha2beta1 cells, although at a lower level as compared to non-treated cells. This may indicate the possible utilization of a PLC independent alternative route via, in this case, the alpha2beta1 integrin.


Coincidence of uterine malformations and endometriosis: a clinically relevant problem?
It is suspected that uterine malformations and endometriosis have a high coincidence. Furthermore, it is expected that obstructive uterine malformations are significantly higher affected than non-obstructive malformations. The correlation between endometriosis and uterine malformations may be due to increased retrograde menstruation, which would explain a higher coincidence of obstructive malformations and endometriosis [14]. This retrospective study investigates whether patients with uterine malformations have a higher prevalence of endometriosis. The study includes patients with uterine malformations who were admitted to our hospital in the period from 01.12.2014 to 30.11.2019. 279 cases were analysed. 263 (94.2%) patients had a non-obstructive uterine malformation, 12 (4.3%) patients had an obstructive uterine malformation and 4 (1.4%) patients had uterine agenesia/hypoplasia. 209 (74.9%) patients had histologically confirmed endometriosis (peritoneal, ovarian or deep infiltrating) and 70 (25.1%) had no endometriosis. In 27 cases, deep infiltrating endometriosis (ENZIAN ABC) was detected additionally to peritoneal and ovarian endometriosis. The study shows a high prevalence of endometriosis in women with uterine malformations. For this reason, endometriosis should always be specifically sought in uterine malformations.


Molecular epidemiology of Brucella abortus strains from cattle in Inner Mongolia, China.
Although the prevalence of brucellosis in Inner Mongolia Autonomous Region currently remains high, data available on the epidemiological of circulating Brucella abortus strains were limited. A total of 75 isolates obtained from cattle, sheep, and humans were analysed using both the classical method and multiple locus variable-number tandem repeat analysis (MLVA). There are at least three B. abortus biovars (1, 3 and 6) in this region, and B. abortus biovar 3 is the predominant one. Ten known MLVA-11 genotypes were identified, of which five genotypes (72, 75, 78, 82 and 210) were shared among strains from this study and others previously collected in two to seven different nations, suggesting that this population has multiple geographic origins. An MLVA-16 assay sorted the 75 B. abortus strains into two groups (I and II), 5 clusters (A-E) and 44 genotypes (GT1-44), with 26 unique genotypes represented by single isolates, indicating that these B. abortus brucellosis cases were not directly epidemiologically related. The remaining 18 shared genotypes (among a total of 47 isolates) were represented by two to eight isolates, suggesting that there were epidemiologically related pathogens from each shared genotype among the cases. Importantly, the cluster B1 branch including 22 cluster isolates with identical or similar genotypes confirmed the occurrence of a concentrated outbreak epidemic in the eastern region during 1988-1995. This work will contribute to better understanding of B. abortus brucellosis epidemiology in Inner Mongolia.


Ipsilateral anterior then irreducible posterior hip dislocation without fracture: a case report.
Anterior hip dislocations and posterior hip dislocations are injuries that commonly result from high-energy trauma. Different mechanisms of injury and forces are typically required for anterior and posterior hip dislocations. We present the case of a patient who sustained an injury that initially resulted in an anterior hip dislocation. After reduction and without experiencing further significant trauma, the patient dislocated posteriorly while being transferred from a stretcher to a table in radiology some 14 hours later. To our knowledge, there have been no such presentations in the literature.


The effect of cadmium pretreatment on the disposition and excretion of methylmercury and trace elements (zinc, copper) in rats.
Cadmium chloride (Cd) was injected s.c. into male rats at a dose rate of 3 mg Cd/kg 3 times a week for 4 weeks. The animals were maintained for administration of methylmercury (203 Hg) chloride at a dose of 3 mg CH3Hg/kg given p.o. 3 times a week for 2 weeks, followed by 3 weeks of recovery period. Animals were sacrificed 24 h after the final dose of MeHg, or 5 weeks after cessation of Cd administration. Cd-pretreatment significantly decreased total Hg concentration in the kidney and RBC and almost completely inhibited demethylation of MeHg in the kidney (from 32% to 3% of inorganic Hg). Cd-pretreatment did not affect urinary excretion of total Hg, but significantly increased daily excretion of total Hg in feces. MeHg given alone significantly increased renal but not hepatic copper levels and decreased copper in the plasma and brain. In Cd-pretreated rats, both renal and hepatic copper concentration were in the normal ranges. Zinc levels in Cd-pretreated rats significantly increased in the kidney, liver and brain but decreased in plasma (compared to control and MeHg-alone treated animals). From these results it can be concluded that Cd-pretreatment may decrease MeHg toxicity by increasing the fecal mercury excretion and by inhibiting the formation of inorganic mercury in the kidney, which is a more potent renal toxin than MeHg.


Assessment of binding indices and physiological responsiveness of the 5-HT2 receptor on human platelets.
This is the first report of parallel studies of binding indices and physiological responsiveness of the "Serotonin-two" (5-HT2) receptor on the human platelet membrane. Binding indices were measured by a microassay employing [125I]ILSD as radioligand and ketanserin to define specific binding. A single receptor population was found, characterized by a KD of 1.69 +/- 0.45 nM and Bmax of 14.5 +/- 6.0 pmol/g protein in healthy subjects. Functional responsiveness of the platelet 5-HT2 receptor complex was assessed by measurement of the extent to which serotonin (10uM) augmented platelet aggregation induced by threshold concentrations of adenosine diphosphate (ADP). A statistically significant positive correlation was found between the number of platelet 5-HT2 receptor sites (Bmax) and the magnitude of the serotonin-amplified aggregation response (r = .70, n = 38, p less than 0.001). Assessment of binding indices and physiological responsiveness of the platelet 5-HT2 receptor complex should facilitate study of age, hormonal, disease, and drug effects on 5-HT2 receptor function in human subjects.


[Intravascular lymphoma revealed by generalized arborescent telangiectasia and repeated venous thrombosis].
Intravascular lymphoma is a rare form of non-Hodgkin's lymphoma characterized by proliferation of lymphoid cells within the lumen of small veins, small arteries and capillaries. A 79-year-old man presented with repeated superficial venous thrombosis of the lower limbs associated with diffuse telangiectasia of the trunk, upper arms and thighs but with normal epidermis. Screening for thrombophilia and neoplasm were negative. The patient subsequently developed abdominal pain, lower-limb oedema, deterioration in performance status and rapidly increasing telangiectasia with the appearance of generalized oedematous cutaneous induration. Increased LDH and anaemia were observed without other blood count anomalies. Intravascular lymphoma was diagnosed on a skin biopsy with telangiectasia and oedema. After eight courses of treatment with rituximab-CHOP the outcome was good. A few telangiectasias associated with nodules or infiltrated plaques are often a clinical manifestation of intravascular lymphoma. The dermatological presentation described here is interesting for two reasons: on the one hand, telangiectasias were initially isolated in normal epidermis without any infiltration for more than one year and, on the other hand, the skin infiltration seen subsequently was very extensive and marked. Moreover, although microthrombi are frequent in small and medium-sized blood vessels, thrombosis of large vessels is rarely described in intravascular lymphoma.


DNA sequencing by denaturation: principle and thermodynamic simulations.
We describe a new DNA sequencing method called sequencing by denaturation (SBD). A Sanger dideoxy sequencing reaction is performed on the templates on a solid surface to generate a ladder of DNA fragments randomly terminated by fluorescently labeled dideoxyribonucleotides. The labeled DNA fragments are sequentially denatured from the templates and the process is monitored by measuring the change in fluorescence intensities from the surface. By analyzing the denaturation profiles, the base sequence of the template can be determined. Using thermodynamic principles, we simulated the denaturation profiles of a series of oligonucleotides ranging from 12 to 32 bases and developed a base-calling algorithm to decode the sequences. These simulations demonstrate that DNA molecules up to 20 bases can be sequenced by SBD. Experimental measurements of the melting profiles of DNA fragments in solution confirm that DNA sequences can be determined by SBD. The potential limitations and advantages of SBD are discussed. With SBD, millions of sequencing reactions can be performed on a small area on a surface in parallel with a very small amount of sequencing reagents. Therefore, DNA sequencing by SBD could potentially result in a significant increase in speed and reduction in cost in large-scale genome resequencing.


Copper ion mediated selective cleavage of C-S bond in ferrocenylthiosemicarbazone forming mixed geometrical [(PPh3)Cu(μ-S)2Cu(PPh3)2] having Cu2S2 core: toward a new avenue in copper-sulfur chemistry.
Unprecedented selective cleavage of the carbon-sulfur bond of the ferrocenylthiosemicarbazone moiety has been observed for the first time, resulting in the formation of mixed geometrical binuclear copper complex [(PPh(3))Cu(μ-S)(2)Cu(PPh(3))(2)]. Upon trying direct synthesis of the title complex, an unusual tetranuclear [Cu(4)(μ(3)-Cl)(4)(PPh(3))(4)] cubane resulted.


Five-Year Changes of Anterior Corneal Indices in Diabetics versus Non-Diabetics: The Shahroud Eye Cohort Study.
To compare 5-year changes of central and peripheral corneal thickness, corneal volume, and keratometry between diabetic and non-diabetic individuals (>40 years) in a population-based study. Right eye corneal indices of the 333 diabetic persons were compared with 2865 non-diabetics. Studied indices included the apical corneal thickness (ACT), minimal corneal thickness (MCT), thickness values on corneal rings of 4 mm, 6 mm, and 8 mm in diameter, the volume of the 10 mm of the corneal diameter, and the central 3 mm keratometry in two steep (Kmax) and flat (Kmin) axes as measured with Pentacam (Oculus, Inc, Lynnwood, WA). In the diabetic and non-diabetic groups, respectively, the 5-year change was +0.1 ± 11.9 and -1.2 ± 11.9 μm (p = 0.035) for ACT, -1.1 ± 12.1 and -2.4 ± 11.9 μm (p = 0.056) for MCT, -3.9 ± 12.6 and -5.1 ± 12.3 μm (p = 0.007) for the 4 mm ring, -5.0 ± 15.3 and -7.5 ± 14.5 μm (p = 0.006) for the 6 mm ring, and -7.0 ± 20.1 and -10.8 ± 19.2 μm (p = 0.011) for the 8 mm ring. The diabetic group showed less reduction in corneal volume (-0.5 ± 1.8 mm3) compared to non-diabetics (-0.8 ± 1.6 mm3) (p = 0.030). Kmax (+0.3 ± 0.5D vs. +0.4 ± 0.5, p = 0.028) and Kmin (+0.4 ± 0.5D vs. +0.5 ± 0.5, p = 0.005) showed less change in diabetics compared to non-diabetics. The overall patterns of change in corneal thickness and shape in over 40-year old diabetics are similar to non-diabetics, such that with aging, reduced thickness and increased keratometry take the cornea towards a prolate shape. However, the age-related changes in central and peripheral corneal thickness, volume and corneal shape are less pronounced in diabetic subjects.


Intramolecular reactions of hydroperoxides and oxetanes: stereoselective synthesis of 1,2-dioxolanes and 1,2-dioxanes.
[reactions: see text] The 5-exo openings of oxetanes by hydroperoxides proceed rapidly and stereospecifically to furnish 1,2-dioxolanes. The corresponding 6-exo cyclizations are slower and proceed with moderate stereoselectivity. In the case of hydroperoxy acetals, 5-exo nucleophilic transfer of alkoxide competes effectively with 6-exo attack by the hydroperoxide.


Tol2-Mediated Delivery of miRNAs to the Chicken Otocyst Using Plasmid Electroporation.
The avian embryo has a well-documented history as a model system for the study of neurogenesis, morphogenesis, and cell fate specification. This includes studies of the chicken inner ear that employ in ovo electroporation, in conjunction with the Tol2 system, to yield robust long-term transgene expression. Capitalizing on the success of this delivery method, we describe a modified version of the Tol2 expression vector that readily accepts the insertion of a microRNA-encoding artificial intron. This offers a strategy to investigate the possible roles of different candidate microRNAs in ear development by overexpression. Here, we describe the general design of this modified vector and the electroporation procedure. This approach is expected to facilitate phenotypic screening of candidate miRNAs to explore their bioactivity in vivo.


Signal transducer and activator of transcription 3 cooperates with androgen receptor/cell cycle-related kinase signalling pathway in the progression of hepatitis B virus infection and gender differences.
The study aimed to investigate the role of androgen receptor (AR)/cell cycle-related kinase (CCRK) signalling pathway in chronic hepatitis B virus (HBV) infection and gender differences, and the contribution of AR regulatory factor signal transducer and activator of transcription 3 (STAT3) in it. AR, CCRK, and phosphorylated STAT3 expressions in liver tissues of chronic HBV-infected patients and non-HBV controls were determined by western blot and compared between genders. The relationships of expression levels with serum HBV DNA levels, liver inflammation activity, and fibrosis score were analysed in chronic HBV-infected patients. The relationships between expression levels of three proteins were also analysed. HBV-infected patients had significantly higher expression levels of AR, CCRK, and p-STAT3Tyr705 compared with controls (p < .01). The expression levels of AR, CCRK, and p-STAT3Tyr705 in chronic HBV-infected patients with severe inflammation were significantly higher than those with mild inflammation (p < .05). Expression levels in patients with heavier fibrosis (stage F4) were higher than in those with less fibrosis (stages F0-3) (p < .01). No gender differences were observed in AR, CCRK, and p-STAT3Tyr705 levels in non-HBV controls; higher levels were observed in HBV-infected males than in HBV-infected females (p < .05). AR, CCRK, and p-STAT3Tyr705 levels in liver tissues positively correlated with each other (p < .0001) and with serum HBV DNA levels (p < .0001). In conclusion, in this study, we first found concordant over-expression of AR, CCRK, and STAT3 in liver tissues of chronic HBV-infected patients who have not yet developed HCC, significantly correlated with the severity of the disease and showed gender differences. STAT3 may be a potential therapeutic co-target for chronic HBV infection.


Breast cancer among Yemeni women using the National Oncology Centre Registry 2004-2010.
In developing countries including Arab countries breast cancer is one of the most common cancers found in women. Even though breast cancer incidence is lower in Arab developing countries than in western countries, Arabic women are more likely to be diagnosed at an earlier age than the women in western countries. A descriptive study was undertaken to investigate the type of breast cancer, lymph node involvement, side of breast and, region and age distribution of breast cancer patients registered in the National Oncology Centre in Yemen. From September 2004 to December 2010, 2654 women across Yemen diagnosed with breast cancer were registered in the National Oncology Centre for treatment. Between the years 2004 and 2010, breast cancer represented 22% of all cancers registered in women. Seventy-one per cent of the women were aged 50 or younger at the time of diagnosis. The most common age group affected was women aged 41-50 years, with (35%) of cases occurring in this age. Invasive ductal carcinoma was the most common pathology (76%) and 79% of the patients had lymph node involvement at the time of diagnosis. Approximately 2% had bilateral disease and the frequency of left (44%) and right breast cancer (42%) were similar. This study has shown that breast cancer is a disease of young women in Yemen. The majority of women presented with lymph node involvement. Hence efforts are needed to increase breast cancer awareness in Yemen for early detection at all age groups, and to target women living in areas that have lower access to health care services.


High-concentration contrast media in multiphasic abdominal multidetector-row computed tomography: effect of increased iodine flow rate on parenchymal and vascular enhancement.
The purpose of this study was to assess the influence of the iodine flow rate on parenchymal and vascular enhancement during multiphasic abdominal multidetector-row computed tomography (MDCT). Fifteen patients underwent MDCT at an iodine flow rate of 1.2 g/s as well as 1.6 g/s (group A, protocols 1 and 2), and 90 patients underwent MDCT at an iodine flow rate of 1.2 g/s (group B) or 1.6 g/s (group C). Measurements were performed for all groups in the liver, spleen, pancreas, portal vein, inferior vena cava, and abdominal aorta. Aortal and pancreatic enhancement during the arterial phase was significantly higher with the higher iodine flow rate. The mean difference in aortal enhancement was 60 Hounsfield units (HU) between protocols 1 and 2 of group A, and the mean difference was 70 HU between groups B and C. The mean difference in pancreatic enhancement was 10 HU between protocols 1 and 2 of group A and 17 HU between groups B and C. During the portal and hepatic venous phases, no significant difference in enhancement was observed. A high iodine flow rate in multiphasic abdominal MDCT improves enhancement of the aorta and the pancreas during the arterial phase but does not influence later phases.


Unexpected maspin immunoreactivity in Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous neuroendocrine tumor, which multifactorial etiopathogenesis seems to be related to ultraviolet radiation, Merkel cell polyomavirus (MCV), and immunosuppression. In this paper, we present three cases of diagnosed MCC in apparently healthy Caucasians, two of them located in a sun-exposed area. They represented 0.25 % of all cutaneous malignant tumors diagnosed in our department. In the first case, MCC was diagnosed in the frontal region of a 67-year-old male, the second case was located in the right thigh of a 55-year-old female, whereas the third case involved the upper trunk of a 62-year-old female. All of these cases were diagnosed in the pT1 stage, having a diameter smaller than 2 cm, but the invasion depth involved the hypodermis. Microscopically, they consisted of small cells with round-oval nuclei having finely dispersed chromatin and well-defined nucleoli. Immunohistochemically, the tumor cells displayed positivity for keratin 20 and neuroendocrine markers, being negative for keratin 7 and S100 protein. Maspin immunoreactivity was seen in cases 1 and 3. Not one of the cases expressed DOG-1 or even TTF-1. Furthermore, this is the first report in literature about maspin positivity in MCC that might be related to sun exposure.


Inhibition of NADPH oxidase prevents advanced glycation end product-mediated damage in diabetic nephropathy through a protein kinase C-alpha-dependent pathway.
Excessive production of reactive oxygen species (ROS) via NADPH oxidase has been implicated in the pathogenesis of diabetic nephropathy. Since NADPH oxidase activation is closely linked to other putative pathways, its interaction with changes in protein kinase C (PKC) and increased advanced glycation was examined. Streptozotocin-induced diabetic or nondiabetic Sprague Dawley rats were followed for 32 weeks, with groups randomized to no treatment or the NADPH oxidase assembly inhibitor apocynin (15 mg . kg(-1) . day(-1); weeks 16-32). Complementary in vitro studies were performed in which primary rat mesangial cells, in the presence and absence of advanced glycation end products (AGEs)-BSA, were treated with either apocynin or the PKC-alpha inhibitor Ro-32-0432. RESULTS; Apocynin attenuated diabetes-associated increases in albuminuria and glomerulosclerosis. Circulating, renal cytosolic, and skin collagen-associated AGE levels in diabetic rats were not reduced by apocynin. Diabetes-induced translocation of PKC, specifically PKC-alpha to renal membranes, was associated with increased NADPH-dependent superoxide production and elevated renal, serum, and urinary vascular endothelial growth factor (VEGF) concentrations. In both diabetic rodents and in AGE-treated mesangial cells, blockade of NADPH oxidase or PKC-alpha attenuated cytosolic superoxide and PKC activation and increased VEGF. Finally, renal extracellular matrix accumulation of fibronectin and collagen IV was decreased by apocynin. In the context of these and previous findings by our group, we conclude that activation of NADPH oxidase via phosphorylation of PKC-alpha is downstream of the AGE-receptor for AGE interaction in diabetic renal disease and may provide a novel therapeutic target for diabetic nephropathy.


Superior oblique myokymia.
Superior oblique myokymia (SOM) is an uncommon, monocular movement disorder involving rapid torsional, low-amplitude contractions of the superior oblique muscle that causes monocular oscillopsia and diplopia. Ocular and neurologic examination in these patients is usually normal, and the clinical course is characterized by exacerbation remissions with good response to medical treatment. In this review, we present recent advances in the pathogenesis of SOM and provide an algorithm for the investigation and management of these patients.


Retinol and tocopherol content in primary and metastatic digestive neoplasms.
Recent trials in digestive-tract cancer have produced conflicting results regarding the protective role of liposoluble vitamins. Accordingly, we have undertaken an extensive appraisal of the behaviour of retinol and tocopherol in both human upper and lower digestive neoplasms. The subjects comprised six healthy controls, 10 patients with symptomatic cholelithiasis, 13 with gastric neoplasms, 12 with colo-rectal neoplasms and 13 with digestive neoplasms and liver metastases. Retinol and tocopherol in the plasma, liver, as well as from secondary malignant nodules of the liver, were determined following a high performance liquid chromatographic technique. The plasma concentration of retinol was significantly reduced only in some neoplastic groups with respect to the non-neoplastic groups. Plasma tocopherol levels remained almost unchanged and, surprisingly, they were higher even in the neoplastic patients and in relation to total serum lipids. There was a sharp decrease in the liver tissue levels of total, mainly esterified, retinol in both cholelithiasis and neoplastic groups; tocopherol, on the other hand, remained more or less unchanged, except in the liver metastatic nodules, where it increased. Levels of plasma vitamin and tissue retinol and tocopherol appear to be unpredictable on the basis of the corresponding circulating levels, and this must be taken into account when prescribing dietary and therapeutic regimes.


The effect of serum from women with preeclampsia on JAR (trophoblast-like) cell line.
Pathologic placentation has been implicated in the pathogenesis of preeclamsia. We sought to assess the effect serum obtained from women with preeclampsia would have on JAR human choriocarcinoma cells regarding growth, invasiveness, and matrix metalloproteinase (MMP) secretion as compared to normotensive pregnant woman. Blood was collected from 11 healthy pregnant women and from10 patients with preeclampsia at 28-33 weeks of gestation. The JAR human choriocarcinoma cell line was cultured in the presence of 10% serum obtained from each group. Cell proliferation, invasiveness, and MMP secretion was measured using a cell proliferation kit, the Matrigel (BD Biosciences, Beit-Ha'Emek, Israel) invasion assay, and gel zymography, respectively. Cell growth increased by 6% when exposed to serum from patients with preeclampsia compared to 30% from controls (P <.01). Trophoblast invasion was significantly (P <.01) reduced in the preeclampsia group (21 +/- 1.9%) compared to controls (27 +/- 2.5%). Valid MMP-2 secretion was reduced by 51% in the preeclampsia group compared to controls (P <.05). Serum obtained from women with preeclampsia contains a factor or factors that exhibit an inhibitory effect on JAR trophoblast cell proliferation, invasiveness, and MMP-2 secretion. These factors may be involved in the pathologic placentation associated with the pathogenesis of preeclampsia.


A concise guide to transtemporal contrast-enhanced ultrasound in children.
Brain contrast-enhanced ultrasound offers insights into the brain beyond the anatomic information offered by conventional grayscale ultrasound. In infants, the open fontanelles serve as acoustic windows. In children, whose fontanelles are closed, the temporal bone serves as the ideal acoustic window due to its relatively smaller thickness than the other skull bones. Diagnosis of common neurologic diseases such as stroke, hemorrhage, and hydrocephalus has been performed using the technique. Transtemporal ultrasound and contrast-enhanced ultrasound, however, are rarely used in children due to the prevalent notion that the limited acoustic penetrance degrades diagnostic quality. This review seeks to provide guidelines for the use of transtemporal brain contrast-enhanced ultrasound in children.


Interaction of dietary composition and PYY gene expression in diet-induced obesity in rats.
The interaction of high-fat diet and the peptide YY (PYY) gene expression in diet-induced obesity and the mechanisms which predisposed some individuals to become obese on high-fat diet were explored. Thirty-six male SD rats were randomly divided into high-fat diet group (n=27) and chow fed control group (n=9). After 15 weeks of either a high-fat diet or chew fed diet, the high-fat diet group was subdivided into dietary induced obesity (DIO) and dietary induced obesity resistant (DIR) group according to the final body weight. Then the DIO rats were subdivided into two groups for a 8-week secondary dietary intervention. One of the group was switched to chew fed diet, whereas the other DIO and DIR rats continued on the initial high-fat diet. Weight gain and food intake were measured, food efficiency was calculated, and the concentrations of plasma neuropeptide Y (NPY) and PYY were assayed. Hypothalamic NPY mRNA expression and PYY mRNA expression in ileum and colon was detected by RT-PCR. The results showed that at the end of 15th week, the levels of body weight and caloric intake were significantly higher in DIO group than in DIR or control group (P<0. 01), while no significant difference was found between DIR and control group (P>0.05). The concentration of plasma PYY was significantly higher in DIR group than in DIO and CF group, while no significant difference was found between DIO and CF group (P <0.01). After switching the DIO rats to chow fed diet, their body weight gains were significantly lower than that of the DIO-HF group. The expression of PYY mRNA was increased in DIO-HF/ CF rats than in DIO-HF rats, and the expression of hypothalamic NPY mRNA was decreased in DIO-HF/CF rats than in DIO-HF group. It was concluded that both dietary composition and PYY gene expression could potently alter the hypothalamic NPY expression and result in different susceptibility to obese and overeating. The decreased PYY was associated with the increased NPY expression and their predisposal to obese and overeating in rats.


The impact of the atrial wall thickness in normal/mild late-gadolinium enhancement areas on atrial fibrillation rotors in persistent atrial fibrillation patients.
Some of atrial fibrillation (AF) drivers are found in normal/mild late-gadolinium enhancement (LGE) areas, as well as moderate ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans. The purpose of this study was to evaluate the impact of the AWT in normal/mild LGE areas on AF drivers. A total of 287 segments in 15 persistent AF patients were assessed. AF drivers were defined as non-passively activated areas (NPAs), where rotational activation was frequently observed, and were detected by the novel real-time phase mapping (ExTRa Mapping), mild LGE areas were defined as areas with a volume ratio of the enhancement voxel of 0% to <10%. The AWT was defined as the minimum distance from the manually determined endocardium to the epicardial border on the LGE-MRI. NPAs were found in 20 (18.0%) of 131 normal/mild LGE areas where AWT was significantly thicker than that in the passively activated areas (PAs) (2.5 ± 0.3 vs. 2.2 ± 0.3 mm, p < .001). However, NPAs were found in 41 (26.3%) of 156 moderate LGE areas where AWT was thinner than that of PAs (2.1 ± 0.2 mm vs. 2.23 ± 0.3 mm, p = .02). An ROC curve analysis yielded an optimal cutoff value of 2.2 mm for predicting the presence of an NPA in normal/mild LGE areas. The location of AF drivers in normal/mild LGE areas might be more accurately identified by evaluating AWT.


Human Papillomaviruses and Skin Cancer.
Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 220 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood.From patients with the rare genetic disorder epidermodysplasia verruciformis (EV) and animal models, evidence is accumulating that cutaneous PV of genus β synergize with ultraviolet (UV) radiation in the development of cutaneous squamous cell carcinoma (cSCC). In 2009, the International Agency for Research on Cancer (IARC) classified the genus β-HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. Epidemiological and biological studies indicate that genus β-PV infection may also play a role in UV-mediated skin carcinogenesis in non-EV patients. However, they rather act at early stages of carcinogenesis and become dispensable for the maintenance of the malignant phenotype, compatible with a "hit-and-run" mechanism.This chapter will give an overview on genus β-PV infections and discuss similarities and differences of cutaneous and genus α mucosal high-risk HPV in epithelial carcinogenesis.


Surgical outcomes of percutaneous endoscopic thoracic decompression in the treatment of multi-segment thoracic ossification of the ligamentum flavum.
Previous studies have demonstrated satisfactory outcomes of percutaneous endoscopic thoracic decompression (PETD) for single-segment thoracic ossification of the ligamentum flavum (TOLF). However, the clinical outcomes of PETD in patients with multi-segment TOLF (mTOLF) remain unclear. The aim of the present study was to evaluate the efficacy and safety of PETD for patients with multi-segment mTOLF. Eighteen consecutive patients (41 segments) with mTOLF were treated with PETD between January 2020 and December 2021. The clinical outcomes were evaluated using the modified Japanese Orthopaedic Association (mJOA) score and Visual Analog Scale (VAS), whereas radiographic parameters were measured by cross-section area of the spinal canal and anteroposterior diameter of the spinal cord. The follow-up period ranged from 14 to 34 months. The mean operation time and blood loss were 154.06 ± 32.14 min and 61.72 ± 12.72 ml, respectively. Hospital stay after first-stage operation was 10.89 ± 2.42 days. The mJOA score and VAS score significantly improved at the final follow-up, with a mean mJOA recovery rate of 63.3 ± 21.90%. The incidence of complications was 12.2% per level. The radiographic outcomes showed adequate decompression of the spinal cord. The present study demonstrates that PETD is effective and safe as a minimally invasive procedure to treat patients with mTOLF. All patients showed relief of their symptoms and improvement in neurological function.


Chitosan-based nanofragrance with antibacterial function applied to wallpaper.
Adding fragrances to the wallpaper can optimize our living environment and office environment. However, the poor adhesion and rapid release of fragrances on wallpapers have limited their application. In this study, vanillin was encapsulated in particles based on chitosan and poly(lactic-co-glycolic acid), thereby achieving a slow release of the fragrance. In addition, due to the addition of chitosan, the adhesion of the fragrance on the wallpaper was enhanced, and the wallpaper was given antibacterial properties.


Abnormalities of serum and plasma components in patients with multiple sclerosis.
Qualitative and quantitative abnormalities in protein and non-protein components of serum and plasma in patients with multiple sclerosis have been the subjects of numerous reports. In this review many of the more recent observations are documented and evaluated. It is concluded that at present the welter of information that has been gathered does not contribute in any major, coherent way to our understanding of the etiology or pathogenesis of the disorder. Several of the abnormalities that have been observed may be future candidates for biochemical markers for multiple sclerosis; at present none is sufficiently reliable, distinctive or easily performed to warrant the status of a useful diagnostic or prognostic test.


The role of ubiquitin-conjugating enzyme Ube2j1 phosphorylation and its degradation by proteasome during endoplasmic stress recovery.
The human Ube2j1 and Ube2j2 are the only ubiquitin-conjugating enzymes (E2s) that are localized to endoplasmic reticulum (ER) through its C-terminal transmembrane domains. Ube2j1 is a known substrate of MAPK signalling pathway and it is phosphorylated at serine-184 during ER stress. Here, we demonstrate that Ube2j1, not Ube2j2 is essential for the recovery of cells from transient ER stress. The ectopic expression of wild-type Ube2j1 and phospho-mimic mutant, Ube2j1S184D but not phospho-mutant Ube2j1S184A can recover cells from ER stress. We also found that ubiquitin-ligase (E3), c-IAP1 preferentially interacts with phosphorylated Ube2j1. Moreover, we noticed that phosphorylated Ube2j1 is rapidly degraded by the proteasome during ER stress cell recovery. Taken together, these data suggest that Ube2j1 and its phosphorylation is important for transient ER stress cell recovery and the phosphorylated Ube2j1 is degraded by the proteasome.


Genetic analysis of the yeast NUD1 endo-exonuclease: a role in the repair of DNA double-strand breaks.
The deoxyribonucleases (DNases) have been shown genetically to be important in the vital processes of DNA repair and recombination. The NUD1 gene, which codes for an endo-exonuclease of Saccharomyces cerevisiae, was analyzed for its role in the DNA double-strand break (DSB) repair processes. While the nud1 strain is only slightly sensitive to ionizing radiation, expression of the HO-endonuclease to introduce a DSB at the MAT locus in that strain results in cell death. Cell survival is inversely proportional to the duration of HO-endonuclease expression. Analysis of the surviving colonies from the nud1 strain indicated that many of the survivors are sterile and that the proportion of these sterile survivors increases with the time of HO-endonuclease expression. On the other hand, the surviving colonies from the isogenic NUD1 strain are mating-proficient. Interestingly, double mutants of nud1 rad52 are more resistant to ionizing irradiation than the rad52 strain and have a cell-survival fraction of 32% for rad52-1 nud1 and 9% for rad52::URA3 nud1 following prolonged HO-endonuclease expression, indicating that nud1 has a suppressor effect on the DSB-induced lethality in rad52. Polymerase chain reaction analysis showed that many of the nud1 survivors contained small alterations within theMAT locus, suggesting that the survivors arose through the process of non-homologous end-joining. These results suggest that the endo-exonuclease acts at a DSB to promote DNA repair via the homologous recombination pathway.


Comprehensive assessment of chrononutrition behaviors among nationally representative adults: Insights from National Health and Nutrition Examination Survey (NHANES) data.
Aligning the time of food intake, i.e., chrononutrition, with the body's circadian clock can have a significant impact on overall health, particularly cardiometabolic health. However, there is a lack of population-based information on various chrononutrition behaviors in the United States, where the prevalence of obesity is high. Our primary aim was to characterize chrononutrition behaviors and their 15-year trends among US adults. We also explored the temporal associations between trends in chrononutrition behaviors and trends in obesity. We utilized data from 8 cycles (2003-2018) of the National Health and Nutrition Examination Survey (NHANES) on 34,470 adults (age >19 years). The clock time of food/beverage consumption was extracted from two 24-h food recalls. The following chrononutrition behaviors were defined: 1) The clock time of the first, last, and midpoint (when 50% of total daily energy was consumed) of food/beverage intake; 2) Eating window (the time elapsed between the first and last intake); 3) Late-night eating (food intake between 21:00-23:59); and 4) Eating frequency. Survey-weighted % or mean ± standard error (SE) was used to demonstrate chrononutrition behaviors and survey-weighted regression models were utilized to evaluate trends in chrononutrition behaviors, BMI, and obesity over a 15-year period. Thirty five percent of US adults had long eating windows lasting 13 h or more, with 59% of individuals consuming calories after 9 PM. The patterns of food intake among American adults were skewed, with the highest proportion of their daily energy intake (36%) being consumed during dinner meals. Notable differences in chrononutrition behaviors observed among different population subgroups. Young adults and men had longer eating windows with a higher prevalence of late-night eating compared to their age- and sex-counterparts. Black individuals had shorter eating periods due to delayed breakfast, the highest proportion (68%) of late-night eating, and obtained a greater amount of energy intake from snacks compared to other racial/ethnic groups. Over the 15-year span, there were only minor changes in a few aspects of chrononutrition behaviors, including 2% reduction in the time of eating window, while most other meal timing behaviors remained unchanged. Trends in chrononutrition behaviors were disproportionately smaller than the trends in obesity rates. US adults persistently consume higher amounts of daily energy intake later in the day. Despite calls for Americans to shift intake to earlier parts of the day, this study shows that there is little change in the overall population over the 15-year period reviewed.


Detection of the common bile duct in difficult bile duct exploration using indocyanine green fluorescence imaging: A case report.
We describe two cases using indocyanine green (ICG) fluorescence imaging for visualization of the common bile duct (CBD) in patients with difficult Bile duct exploration (BDE) due to extensive dense adhesions around the hepatoduodenal ligament. The CBD was rapidly detected under fluorescence guidance without excessive dissection of extensive dense adhesions. It is illustrated that the use of ICG fluorescence imaging is effective and feasible for detecting the CBD and thus we highly recommend this method during difficult BDE.


Predominance of hybrid discrete typing units of Trypanosoma cruzi in domestic Triatoma infestans from the Bolivian Gran Chaco region.
In the Gran Chaco region the reinfestation by Triatoma infestans remains a major problem for control of Chagas disease. Trypanosoma cruzi the agent of the illness presents a broad genetic intraspecific variability which is poorly documented in the Bolivian Gran Chaco. This work presents the identification of the discrete typing units (DTUs) currently recognized for T. cruzi in T. infestans populations collected before and after residual insecticide spraying in four villages in this region. Before spraying, of 84 samples, the frequencies of the DTUs identified by using the multiplex PCR based on the non transcribed spacer of the mini-exon gene (MMPCR) were 0.21 for TcI, 0.70 for TcII/TcV/TcVI, and 0.17 for TcIII/TcIV and no significant difference was observed after spraying (76 samples). Moreover 13% of the total sample corresponds to T. infestans specimens with mixed infection of DTUs of which three were TcII/TcV/TcVI with TcIII/TcIV. The partial sequences of T. cruzi Gpi gene obtained from 14 PCR products agree the MMPCR DTU identification and allowed to precise the occurrence of TcIII, TcII and hybrid TcV/TcVI stocks which were not discriminated by the MMPCR. Given the high prevalence of hybrid stocks, the authors ask whether the recombination event at the origin of hybrids would have taken place in the Gran Chaco where the putative parents are also present.


Diagnostic laparoscopy.
Diagnostic laparoscopy is a powerful tool in the surgeon's armamentarium when used appropriately. There is a low complication rate and high diagnostic sensitivity. In addition to conventional operating room procedures, this technique can be applied in a variety of other settings, often without general anesthesia. Many patients can be spared invasive nontherapeutic laparotomies particularly in the area of trauma and cancer diagnosis. The surgeon must become a superior visual anatomist in order to be able to take maximum advantage of this technique.


Stereotactic biopsy for intracranial lesions: reliability and its impact on the planning of treatment.
The authors present a retrospective analysis of 308 computed tomography (CT)-guided stereotactic biopsies in 300 patients in order to evaluate the reliability and efficacy of the stereotactic biopsy for intracranial lesions. All patients were suffering from undetermined intracranial lesions and treated at Seoul National University Hospital between January 1993 and December 1999. Age ranged from three to 79 years (mean 41); the male to female ratio was 180:120. All patients underwent CT-guided stereotactic biopsy for the histological verification and/or evacuation of the cyst using Riechert-Mundinger stereotactic system. Histological diagnosis was made in 275 patients (diagnostic yield 91.7%). Diagnostic yield was better in group with frozen section examination during the stereotactic procedure than the group without it (p=0.01). Neoplastic lesions were more likely to be diagnosed in stereotactic biopsy than non-neoplastic lesions (p=0.02). Among 30 patients who underwent craniotomy after the stereotactic biopsy, the histological diagnoses after the craniotomy were identical to those of the stereotactic biopsy in 29 patients (diagnostic accuracy 96.7%). Two patients died within seven days after the stereotactic biopsy (mortality 0.6%). The postoperative new neurological deficit or aggravation of the neurological status was found in 19 patients, including transient cases of seven patients (permanent morbidity rate 3.9%). Histologically malignant gliomas and deeply-located lesions were the significant risk factors for the development of complications. In 148 cases, histological diagnosis of the stereotactic biopsy was different from the preoperative clinical diagnosis. Among these cases, the treatment plan was changed after stereotactic biopsy in 81 cases. Stereotactic biopsy for intracranial lesions is a reliable and relatively safe procedure. It is also a very efficacious method especially in patients who need histological confirmation for the treatment.


Analysis of Tumor Necrosis Factor Function Using the Resonant Recognition Model.
The tumor necrosis factor (TNF) is a complex protein that plays a very important role in a number of biological functions including apoptotic cell death, tumor regression, cachexia, inflammation inhibition of tumorigenesis and viral replication. Its most interesting function is that it is an inhibitor of tumorigenesis and inductor of apoptosis. Thus, the TNF could be a good candidate for cancer therapy. However, the TNF has also inflammatory and toxic effects. Therefore, it would be very important to understand complex functions of the TNF and consequently be able to predict mutations or even design the new TNF-related proteins that will have only a tumor inhibition function, but not other side effects. This can be achieved by applying the resonant recognition model (RRM), a unique computational model of analysing macromolecular sequences of proteins, DNA and RNA. The RRM is based on finding that certain periodicities in distribution of free electron energies along protein, DNA and RNA are strongly correlated to the biological function of these macromolecules. Thus, based on these findings, the RRM has capabilities of protein function identification, prediction of bioactive amino acids and protein design with desired biological function. Using the RRM, we separate different functions of TNF as different periodicities (frequencies) within the distribution of free energy electrons along TNF protein. Interestingly, these characteristic TNF frequencies are related to previously identified characteristics of proto-oncogene and oncogene proteins describing TNF involvement in oncogenesis. Consequently, we identify the key amino acids related to the crucial TNF function, i.e. receptor recognition. We have also designed the peptide which will have the ability to recognise the receptor without side effects.


New posteromedial portal for ankle arthroscopy.
We describe a new posteromedial portal through the bed of the posterior tibial tendon. It can be made easily with a 0.5-inch posteromedial skin incision along the course of the posterior tibial tendon just behind the posterior colliculus of the medial malleolus. After the flexor retinaculum is incised and the posterior tibial tendon is retracted anteriorly, a small bulging area of capsule can be seen as a result of saline inflation. The new posteromedial portal can then be made easily through this inflated capsule. This portal allows good access to the posterior joint surface and has a minimal risk of injury to the medial neurovascular bundle.