Early Administration of Anti-SARS-CoV-2 Monoclonal Antibodies Prevents Severe COVID-19 in Kidney Transplant Patients.
Kidney transplant recipients (KTRs) are prone to develop severe COVID-19 and are less well protected by vaccine than immunocompetent subjects. Thus, the use of neutralizing anti-SARS-CoV-2 monoclonal antibody (MoAb) to confer a passive immunity appears attractive in KTRs. We performed a French nationwide study to compare COVID-19-related hospitalization, 30-day admission to intensive care unit (ICU), and 30-day death between KTRs who received an early infusion of MoAb (MoAb group) and KTRs who did not (control group). Controls were identified from the COVID-SFT registry (NCT04360707) using a propensity score matching with the following covariates: age, sex, delay between transplantation and infection, induction and maintenance immunosuppressive therapy, initial symptoms, and comorbidities. A total of 80 KTRs received MoAb between February 2021 and June 2021. They were matched to 155 controls. COVID-19-related hospitalization, 30-day admission to ICU, and 30-day death were less frequently observed in the MoAb group (35.0% vs. 49.7%, P = 0.032; 2.5% vs. 15.5%, P = 0.002; 1.25% vs. 11.6%, P = 0.005, respectively). No patient required mechanical ventilation in the MoAb group. The number of patients to treat to prevent 1 death was 9.7. The early use of MoAb in KTRs with a mild form of COVID-19 largely improved outcomes in KTRs.


[Relationship between genetic polymorphisms of IRF6 rs642961 and nonsysdromic cleft lip with or without cleft palate].
To explore the relationship between polymorphism of interferon regulatory factor 6 (IRF6) gene rs642961 locus and nonsyndromic cleft lip with or without cleft palate (NSCL ± P). There were 88 NSCL ± P nuclear families and 116 healthy people as control recruited from Chinese northern area. The polymorphism of IRF6 rs642961 locus was detected by tetra-primer amplification refractory mutation system-polymerase chain reaction (tetra-primer ARMS-PCR). Case-control analysis, transmission-disequilibrium test (TDT), haplotype-based haplotype relative risk analysis (HHRR) and family-based association test (FBAT) were carried out. There was significant difference in rs642961 of IRF6 locus between the NSCL P group and control group, whether in children or parents (P < 0.05). The odds ratio (OR) of AG and AA versus GG is above one, and its 95% confidence interval did not include 1 in offspring, father and mother group, which meant genetic variant of rs642961 of IRF6 could increase the risk of occurrence of NSCL ± P. The allele transmission disequilibrium for rs642961 of IRF6 variant in NSCL ± P families was found by TDT analysis (P < 0.05). HHRR calculation also showed that there was association between the genetic variant and the occurrence of NSCL ± P (P < 0.05). While FBAT test showed that there was relationship between the genetic variant and the occurrence of NSCL ± P in addictive model. Polymorphism IRF6 gene locus is associated with NSCL ± P in northern Chinese population.


Varicella-zoster virus ORF 58 gene is dispensable for viral replication in cell culture.
Open reading frame 58 (ORF58) of varicella-zoster virus (VZV) lies at the 3'end of the Unique long (UL) region and its functional is unknown. In order to clarify whether ORF58 is essential for the growth of VZV, we constructed a deletion mutant of ORF58 (pOka-BACDelta58) from the Oka parental genome cloned into a bacterial artificial chromosome (pOka-BAC). The ORF58-deleted virus (rpOkaDelta58) was reconstituted from the pOka-BACDelta58 genome in MRC-5 cells, indicating that the ORF58 gene is non-essential for virus growth. Comparison of the growth rate of rpOkaDelta58 and recombinant wild-type virus by assessing plaque sizes revealed no significant differences between them both in MRC-5 cells and malignant melanoma cells. This study shows that the ORF58 gene is dispensable for viral replication and does not affect the virus' ability to form plaques in vitro.


Association of higher arterial ketone body ratio (acetoacetate/β-hydroxybutyrate) with relevant nutritional marker in hemodialysis patients.
An association of higher levels of β-hydroxybutyrate (β-HB) in serum with greater mortality in hemodialysis (HD) patients has been reported. This study examined the significance of arterial ketone body ratio (AcAc/β-HB), a relevant marker of energy state, in HD patients. The levels of arterial AcAc and β-HB, and AcAc/β-HB ratio were determined in 49 HD patients just before undergoing an HD session. Additionally, changes in those levels during the session were examined to investigate their associations with clinical nutritional markers. Arterial β-HB, but not AcAc, was significantly higher at the baseline in 25 patients with type 2 diabetes mellitus (T2DM) as compared to 24 non-DM patients, with a significant reduction in arterial AcAc/β-HB ratio seen in those with DM. Although the arterial AcAc/β-HB ratio before the HD session was significantly higher in the non-DM group, it did not differ significantly after the session between the groups, indicating a faster rate of β-HB disappearance from circulation in non-DM HD patients during the interdialytic period. Multiple regression analysis, which included age, gender, presence/absence of DM, log HD duration, log β-HB, and log AcAc/β-HB ratio as independent variables, revealed an independent and significant association of log AcAc/ β-HB ratio, but not log β-HB, with serum albumin and uric acid. We found that a decreased AcAc/β-HB ratio resulting from increased β-HB, but not increased β-HB itself, was a significant factor independently associated with decreased levels of serum albumin and uric acid, known to be related to higher mortality in HD patients. Furthermore, it is possible that higher mortality in DM HD patients can be explained by reduced arterial AcAc/β-HB ratio.


Computerized analysis of tissue density effect on missed cancer detection in digital mammography.
This paper presents a study of the analysis of breast density in missed cancer cases and the effect of tissue density on cancer detection. A total of 100 missed cancer cases were collected. The breast density tissue was segmented with a statistical-based method. A set of tests was then applied to examine: (1) the differences in density between the mammograms at the detected stage and that at missed stage; (2) the density difference between the cancerous mammograms and their contra-lateral normal mammograms in the missed cancer cases; (3) the effect of breast density on CAD cancer detection. The results demonstrate that breast density is an important factor affecting not only radiologist's reading but also CAD performance. In order to improve early detection of breast cancer, a special effort should be directed to the high dense breast cases in CAD system design.


Lack of an association between apolipoprotein E epsilon 4 and Alzheimer's disease in elderly Nigerians.
As part of a community-based study of Alzheimer's Disease (AD) in a Nigerian population aged 65 years and over, we have determined apolipoprotein E (APOE) genotypes on 56 subjects (39 controls and 17 subjects with dementia, including 12 with AD). The epsilon 4 allele of APOE was not associated with AD or dementia in this community-based sample. The epsilon 4 allele frequency was 17.6% in demented patients and 16.7% in AD patients compared with 20.5% in the control subjects. These findings are in marked contrast to the strong association between the epsilon 4 allele and AD in our previously reported study with African Americans.


Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos.
Base editors have substantial promise in basic research and as therapeutic agents for the correction of pathogenic mutations. The development of adenine transversion editors has posed a particular challenge. Here we report a class of base editors that enable efficient adenine transversion, including precise A•T-to-C•G editing. We found that a fusion of mouse alkyladenine DNA glycosylase (mAAG) with nickase Cas9 and deaminase TadA-8e catalyzed adenosine transversion in specific sequence contexts. Laboratory evolution of mAAG significantly increased A-to-C/T conversion efficiency up to 73% and expanded the targeting scope. Further engineering yielded adenine-to-cytosine base editors (ACBEs), including a high-accuracy ACBE-Q variant, that precisely install A-to-C transversions with minimal Cas9-independent off-targeting effects. ACBEs mediated high-efficiency installation or correction of five pathogenic mutations in mouse embryos and human cell lines. Founder mice showed 44-56% average A-to-C edits and allelic frequencies of up to 100%. Adenosine transversion editors substantially expand the capabilities and possible applications of base editing technology.


Determination of cortisol in human plasma by radioimmunoassay. Use of the 125I-labelled radioligand.
A radioimmunoassay for plasma cortisol featuring the gamma-emitting radioligand 125I-iodohistamine, coupled to cortisol-3-(O-carboxymethyl)-oxime, is described. The new procedure retains much of the specificity associated with the use of anti-cortisol-3-BSA sera with tritium-labelled radioligands, and has the further advantages that running costs are lower and there is a greater potential for automation. Cortisol values obtained by this procedure agree well with those obtained by a published specific radioimmunoassay using the tritiated cortisol radioligand. Specificity of the procedure was checked by comparing values obtained with and without thin-layer chromatography purication: correlation was excellent (r = 0.96). Satisfactory levels of sensitivity, precision, and accuracy were obtained.


Micro- and Nanoscale Technologies for Delivery into Adherent Cells.
Several recent micro- and nanotechnologies have provided novel methods for biological studies of adherent cells because the small features of these new biotools provide unique capabilities for accessing cells without the need for suspension or lysis. These novel approaches have enabled gentle but effective delivery of molecules into specific adhered target cells, with unprecedented spatial resolution. We review here recent progress in the development of these technologies with an emphasis on in vitro delivery into adherent cells utilizing mechanical penetration or electroporation. We discuss the major advantages and limitations of these approaches and propose possible strategies for improvements. Finally, we discuss the impact of these technologies on biological research concerning cell-specific temporal studies, for example non-destructive sampling and analysis of intracellular molecules.


[Giant cell arteritis: Role of color-duplex ultrasound].
Giant cell arteritis is the most common primary vasculitis of large-vessel occurring in subjects over 50 years of age. Many imaging techniques has been evaluated to improve the diagnosis of giant cell arteritis. Among these imaging techniques, ultrasound has shown good performances to detect inflammatory involvement of the temporal arteries as well as branches of the aorta. Several publications and recent EULAR recommendations have emhasized the place of this tool in the diagnosis of giant cell arteritis.


Single-change items did not measure change in quality of life.
The aim of this study was to demonstrate validity for the two items in the Veterans RAND 36 Item Health Survey (VR-36) that attempt to measure the change in health-related quality of life (HRQOL) over 1 year, using serial administrations of the full instrument as a gold standard. A total of 1,117 subjects in the Veterans Health Study completed the VR-36 instrument at study inception and 1 year later. Using nonparametric correlation and factor analyses, we compared the single-change items (SCIs) with 1-year changes in the physical component score (PCS) and mental component score (MCS), the summary scores of the VR-36. We found low correlations between the SCI and longitudinal changes in the PCS (0.21) and MCS (0.18) and moderate correlations between the SCI and the current PCS (0.50) and MCS (0.41). Factor analyses confirmed that the SCI loaded highly with current HRQOL. The two SCIs contained in the VR-36, which are intended to measure changes in health over the past year, are more highly correlated with current self-reported HRQOL. In this instrument, single-item measurements of health status change cannot be substituted for changes in serial measures of HRQOL.


Neural substrates of sensory-guided locomotor decisions in the rat superior colliculus.
Deciding in which direction to move is a ubiquitous feature of animal behavior, but the neural substrates of locomotor choices are not well understood. The superior colliculus (SC) is a midbrain structure known to be important for controlling the direction of gaze, particularly when guided by visual or auditory cues, but which may play a more general role in behavior involving spatial orienting. To test this idea, we recorded and manipulated activity in the SC of freely moving rats performing an odor-guided spatial choice task. In this context, not only did a substantial majority of SC neurons encode choice direction during goal-directed locomotion, but many also predicted the upcoming choice and maintained selectivity for it after movement completion. Unilateral inactivation of SC activity profoundly altered spatial choices. These results indicate that the SC processes information necessary for spatial locomotion, suggesting a broad role for this structure in sensory-guided orienting and navigation.


Neonatal melatonin administration advances rat vaginal opening and disrupts estrous cyclicity and estrogen-dependent regulatory mechanisms of luteinizing hormone and prolactin.
Melatonin (100 micrograms/rat) was administered to female rats on day 5 of life, 3 hours prior to the onset of darkness or at 12:00 hours. Melatonin administration induced precocious puberty in both cases, as indicated by the advance of the time of the vaginal opening and the appearance of the first estrous smear as compared with controls (P less than 0.01), together with an increase in the number of estrous smears (P less than 0.05) and a reduction in the number of diestrous smears (P less than 0.05). Decreased serum prolactin levels were observed on day 21 of age (P less than 0.05) in melatonin-treated rats with both of the melatonin injection times as compared with controls. No differences were apparent in basal luteinizing hormone (LH) levels either at 30 or at 60 days of age comparing melatonin- and vehicle-treated rats with either of the scheduled melatonin injection times. As to serum follicle-stimulating levels (FSH) levels, there was a marked decrease in circulating FSH levels in melatonin-treated rats in both cases on days 21, 30, and 45 (P less than 0.05) as compared with controls. A marked increase of serum prolactin at both 48 and 55 hours after estradiol benzoate (EB) administration was detected in 30-day-old melatonin-treated rats as compared with controls (P less than 0.05 for both points). Also, an increased responsiveness of prolactin to EB was found on the first day post-administration. At 60 days of age, an increase in prolactin responses to EB was observed on the first day post-administration (31 and 48 hours after, (P less than 0.01), whereas no differences were detected at any other studied time. The LH burst that occurs 31 hours after EB administration in 30-day-old rats was decreased in melatonin-treated animals as compared with controls (P less than 0.05). In 60-day-old melatonin-treated rats, a marked increase in the LH response to EB administration, 31 hours after injection (P less than 0.01), was observed. These data suggest that neonatal melatonin administration in pharmacological amounts induces precocious puberty as measured by vaginal opening and, furthermore, it advances the appearance of the first estrous smear with age-dependent modifications of estrous cyclicity and prolactin and LH responses to EB.


Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents.
High dose estrogens (HDEs) were frequently used as endocrine agents prior to the introduction of tamoxifen which carries fewer side effects. Due to the development of resistance to available endocrine agents in almost all women with metastatic breast cancer, interest has renewed in the use of HDEs as yet another endocrine option that may have activity. We report our experience with one of the HDEs ("ethinylestradiol" 1 mg daily) in advanced breast cancer (locally advanced and metastatic) in post-menopausal women who had progressed on multiple endocrine agents. According to a database of advanced breast cancer patients seen in our Unit since 1998, those who had complete set of information and fulfilled the following criteria were studied: (1) patients in whom further endocrine therapy was deemed appropriate i.e., patients who have had clinical benefit with previous endocrine agents or were not fit or unwilling to receive chemotherapy in the presence of potentially life-threatening visceral metastases; (2) disease was assessable by UICC criteria; (3) were treated with "ethinylestradiol" until they were withdrawn from treatment due to adverse events or disease progression. Twelve patients with a median age of 75.1 years (49.1-85 years) were identified. Majority (N = 8) had bony disease. They had ethinylestradiol as 3rd to 7th line endocrine therapy. One patient (8%) came off treatment early due to hepato-renal syndrome. Clinical benefit (objective response or durable stable disease for > or = 6 months) was seen in 4 patients (33.3%) with a median duration of response of 10+ (7-36) months. The time to treatment failure was 4 (0.5-36) months. Yet unreported, high dose "ethinylestradiol" is another viable therapeutic strategy in heavily pre-treated patients when further endocrine therapy is deemed appropriate. Although it tends to carry more side effects, they may not be comparable to those of other HDEs (such as diethylstilbestrol) or chemotherapy.


An objective assessment of the sudomotor response after thoracoscopic sympathectomy.
Thoracoscopic sympathectomy has become an accepted therapeutic option for palmar hyperhidrosis. Objective assessment of sweat output after sympathectomy, however, has not been reported to date. We report for the first time sweat output measurements after sympathectomy during a 3-year postoperative period. Thoracoscopic sympathectomy was performed by division of T2 and T3 sympathetic ganglia in 17 healthy adult patients with no comorbidities. Preoperative and postoperative sweat measurements were done at 29 degrees C (below sweat threshold, at baseline, after conversation, and after a mental arithmetic challenge) and at 40 degrees C (baseline and after exercise) with the ventilated capsule technique in left palm, sole, and chest wall. Serial postoperative measurements were conducted at 1 and 6 months and 1, 2, and 3 years. Sweat output fell significantly after sympathectomy relative to preoperative levels under all experimental conditions (P < .001, analysis of variance) in the left palm. Differences in sweat outputs in the left palm were statistically significant between groups at baseline and postoperatively after mental arithmetic challenge and exercise at 40 degrees C (P < .05, analysis of variance). Compensatory increases in the sweat outputs from the left sole and chest were observed after sympathectomy. No patients had recurrence of preoperative sweat output values at follow-up. According to objective sweat output measurements, thoracoscopic sympathectomy results in long-term control of palmar hyperhidrosis. This evaluation method is valuable in investigating recurrence of symptoms or compensatory hyperhidrosis after sympathectomy, providing a robust and objective criterion for planning intervention.


Sitravatinib is a potential EGFR inhibitor and induce a new death phenotype in Glioblastoma.
Glioblastoma (GBM) is a highly lethal neurological tumor that presents significant challenge for clinicians due to its heterogeneity and high mortality rate. Despite extensive research, there is currently no effective drug treatment available for GBM. Research evidence has consistently demonstrated that the epidermal growth factor receptor (EGFR) promotes tumor progression and is associated with poor prognosis in several types of cancer. In glioma, EGFR abnormal amplification is reported in approximately 40% of GBM patients, with overexpression observed in 60% of cases, and deletion or mutation in 24% to 67% of patients. In our study, Sitravatinib, a potential EGFR inhibitor, was identified through molecular docking screening based on protein structure. The targeting of EGFR and the tumor inhibitory effect of Sitravatinib on glioma were verified through cellular and in vivo experiments, respectively. Our study also revealed that Sitravatinib effectively inhibited GBM invasive and induced DNA damage and cellular senescence. Furthermore, we observed a novel cell death phenotype induced by Sitravatinib, which differed from previously reported programmed death patterns such as apoptosis, pyroptosis, ferroptosis, and necrosis.


Echocardiography in experimentally-induced myocardial ischemia.
Using an experimental canine model, we have employed echocardiography to study segmental dyskinesis produced by acute coronary occlusion. Characteristic alterations in posterior wall and septal motion occur after acute coronary ligation; these resemble clinical abnormalities described in acute and old myocardial infarction. The degree of dyskinesis produced is directly related to the severity of the perfusion deficit. Coronary reperfusion had variable effects on dyskinesis; most animals showed improvement but in some the myocardial contraction abnormalities became more severe. A vaviety of interventions were undertaken during ischemia. The elevated level of arterial pressure induced by the administration of methoxamine increased ventricular diameter and presumably oxygen requirements, and was deleterious to ischemic wall motion whereas the administration of norpinephrine reduced ventricular diameter and improved function. Intra-aortic balloon counterpulsation had little effect on either ischemic motion or perfusion. These experimental studies generally support conclusions drawn from clinical echocardiograms about the relationship of abnormalities of wall motion to coronary artery lesions and myocardial ischemia, and suggest further clinical uses for echocardiography in coronary disease.


Modulation of cortisol metabolism during treatment of acromegaly is independent of body composition and insulin sensitivity.
The set point of cortisol-cortisone conversion is shifted in the direction of cortisone by the inhibition of the activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) during adult GH replacement and in active acromegaly. Additionally, both fat mass and insulin may modulate 11beta-HSD1 and are both influenced by changes in GH status. This study examined the relative direct contribution of GH/IGF1 in modulating cortisol metabolism. Overall cortisol/cortisone conversion (ratio of urine 11-hydroxy-/11-oxo-cortisol metabolites; Fm/Em), insulin sensitivity (homeostatic model assessment; HOMA %S) and fat mass (DXA) were examined in parallel in 6 patients (mean age 53 years, range 42-76; 4 males, 2 females) with previously untreated active acromegaly during 6 months of therapy with Sandostatin LAR (20-30 mg i.m. 4 weekly). All but 1 patient had normal ACTH reserve. At baseline, Pearson correlation demonstrated an inverse relationship between serum GH (mean of a 5-point day curve) and Fm/Em (r = -0.83, p = 0.04) and a trend towards an inverse relationship between HOMA %S and Fm/Em (r = -0.79, p = 0.06) but no other patterns were evident. During the course of treatment, serum GH decreased from 9.9 +/- 6.4 (mean +/- SD) to 3.5 +/- 3.1 ng/ml (p < 0.01) and serum IGF-1 from 785 +/- 268 to 431 +/- 156 ng/ml (p < 0.005). Fm/Em increased from 0.52 +/- 0.1 to 0.75 +/- 0.08 (p < 0.03) consistent with increased 11beta-HSD1 activity. There were no significant changes in truncal fat percentage (33.0 +/- 9.0 vs. 33.0 +/- 8.2) or insulin sensitivity (HOMA %S: 37.1 +/- 8.6 vs. 52.8 +/- 33.7). Modulation of cortisol metabolism during treatment of active acromegaly is dependent on changes in GH/IGF-1 status and is not influenced by any individual change in body composition or insulin sensitivity.


Neuromuscular Weakness in Intensive Care.
Diseases of the peripheral nervous system create an additional diagnostic conundrum within the intensive care setting. Causes are vast, presentations are myriad, and symptoms are often ill-defined or misidentified. Care benefits from a multidisciplinary approach including a neuromuscular specialist, rehabilitation services, and a specialty pharmacist in addition to the neurocritical care team. In general, survivors achieve a good functional recovery relative to their preintensive care unit baseline.


Establishment and characterization of a new conditionally immortalized human astrocyte cell line.
Astrocytes are the most abundant cell types in mammalian brains, within which they participate in various neuronal activities, partly by utilizing the numerous transporters expressed at their plasma membranes. Accordingly, detailed characterization of astrocytic functions, including transporters, are essential for understanding of mechanistic basis of normal brain functions, as well as the pathogenesis and treatment of various brain diseases. As a part of overall efforts to facilitate such studies, this study reports on the establishment of a new human astrocyte cell line, which is hereafter referred to as human astrocyte/conditionally immortalized, clone 35 (HASTR/ci35). This line, which was developed utilizing a cell immortalization method, showed excellent proliferative ability and expressed various astrocyte markers, including glial fibrillary acidic protein. When co-cultured with neuronal cells, HASTR/ci35 cells could facilitate their dendritic network formation. Furthermore, HASTR/ci35 cells not only possessed significant glutamate and adenosine transporter activities but also exhibited organic ion transporter activities. To summarize, HASTR/ci35 cells possess several key astrocytic characteristics, including various transporter functions, while simultaneously showing infinite proliferation and scalability. Based on these findings, HASTR/ci35 cells can be expected to contribute significantly to various human astrocyte study fields. In vitro astrocyte models are valuable experimental tools in various astrocyte studies. Here, we report the establishment of a new human astrocyte cell line, HASTR/ci35, which show various key astrocyte properties, including astrocytic transporter activities, glycogen storage and facilitation of neuronal cell differentiation. Thus, HASTR/ci35 is expected to significantly contribute to advances toward detailed understanding of human astrocyte functions.


Comparative effects of polystyrene nanoplastics with different surface charge on seedling establishment of Chinese cabbage (Brassica rapa L.).
Micro- and nano-plastics are common emerging pollutants of great interest. However, the impacts of them on terrestrial plants were still poorly understood. In this study, comparative effects of exposure of polystyrene nanoplastics (PS) and amino-modified polystyrene nanoplastics (PS-NH2) on Chinese cabbage (Brassica rapa L.) plants at different growth stages were investigated. Hydroponically cultured seedlings were exposed to PS and PS-NH2 at 0, 1, 10, and 100 mg/L at skotomorphogenesis stage for 48 h, photomorphogenesis stage for 18 h, and the whole stage, respectively. Results showed that both PS and PS-NH2 had no discernible effect on radicle elongation at the skotomorphogenesis stage whereas significantly (P < 0.05) reduced photosynthetic pigment contents in varying degrees (18.06%-28.52%, 22.46%-36.86%) at the photomorphogenesis stage and the whole stage. Moreover, there was no significant difference between PS treatments and control except the 26.52% decline of chlorophyll a content at 1 mg/L at photomorphogenesis, while PS-NH2 significantly (P < 0.05) decreased photosynthetic pigment contents except the chlorophyll b content at 10 mg/L at photomorphogenesis. The content of chlorophyll a decreased by 26.68% for the PS-NH2-treated group and 22.46% for the PS-treated group at 1 mg/L during the whole stage. Results manifested that less negatively charged PS-NH2 seemed to show more severe phytotoxicity both at the photomorphogenesis stage and the whole stage. Notably, the surface charge of nano-plastics and the integrity of seedling establishment could be the main factors impacting the above difference. These findings are expected to improve our understanding of the effects of PSNPs on crop plants.


Ultrasonic-assisted sustainable extraction and dyeing of organic cotton fabric using natural dyes from Dillenia indica leaf.
As a means of preventing environmental damage caused by synthetic dyes, eco-friendly textile dyeing with natural dyes is gaining popularity worldwide. This study focused on the extraction of dyes from the leaf of Dillenia indica (D. indica) tree using an ultrasonic extraction technique and applied on the organic cotton fabrics. The ultrasonic method was used for both extractions of D. indica dyes and dyeing of organic cotton fabrics. Here, the amount of D. indica powder used were 5% and 6.67% for producing light and dark shade, respectively. The investigation of the color fastness to washing, rubbing, and light for the dyed organic cotton fabrics indicated an excellent rating. The spectrophotometric analysis revealed the L* (lightness or darkness), a* (redness or greenness), b* (yellowness or blueness), C* (chroma), h* (hue), R% (reflectance), and K/S (color strength) values, which accurately represented the shade of the dyed organic cotton fabric. To understand the interaction between D. indica dye and organic cotton fabrics, different characterization including, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were performed. The characterization outcomes confirmed the successful deposition of D. indica dyes on the organic cotton fabrics. The other comparable testing results such as bursting strength, air permeability, and thermogravimetric analysis (TGA) of dyed and undyed organic cotton fabrics were in the acceptable range. One of the important findings of this research was no chemicals were utilized during the extraction and dyeing of organic cotton fabrics. This process can be referred to as completely chemical-free and advantageous for the environment because no chemicals were needed during extraction or dyeing. Therefore, the natural dye extracted from D. indica is extremely promising and could be a viable option for the sustainable dyeing of cotton fabrics in the textile dyeing industry.


Intracranial Mimics of Cauda Equina Syndrome: Heads or Tails?
To report cases of extraspinal mimics of cauda equina syndrome (CES) to enable prompt diagnosis and treatment in the future. CES results from compression of spinal nerve roots. Current practice mandates lumbosacral magnetic resonance imaging (MRI) scanning to diagnose CES. However, it may not reveal compression or provide an explanation for the presentation. We present 3 cases of suspected CES who went on to have intracranial pathology. Retrospective review of all patients presenting with CES-type features who were subsequently found to have causative intracranial pathology over a 6-month period. Three cases were found, and these are hereby presented. Case 1: A 57-year-old lady presented with urinary retention and bilateral leg weakness. She underwent an MRI spine which showed no evidence of CES. She was diagnosed with haemorrhagic intracranial metastases. Case 2: A 52-year-old lady presented with lower back and right buttock pain, with right-sided leg numbness, saddle hypoesthesia, and bowel and bladder incontinence. MRI spine showed no cauda equina compression. MRI neuraxis revealed a subdural haematoma. Case 3: A 69-year-old lady presented with a 6-day history of urinary incontinence, right foot drop, and leg weakness. MRI spine was negative for CES. She was diagnosed with an intraparenchymal haematoma of posterior left frontal lobe. Negative lumbosacral MRI will not exclude extraspinal mimics of CES and, although rare, these cases should be considered.


Evaluation of Congenital Valvular Heart Diseases by the Pediatrician: When to Follow, When to Refer for Intervention?
Isolated congenital valvular heart disease in children constitutes a small fraction of congenital heart diseases. Valve involvement is seen more along with other congenital diseases. The most commonly involved valve is the pulmonary valve followed by the aortic valve. Stenotic lesions of the pulmonary and aortic valves are more frequently encountered than mitral and tricuspid valvular lesions. The presentation depends on the severity of the lesion and the age of the patient. Symptoms range from asymptomatic status to florid symptoms of valve obstruction and/or leak. Detailed clinical assessment and various imaging techniques confirm the diagnosis and help in management planning. Transcatheter balloon dilatation for obstructive pulmonary valve has very good long-term outcomes. The results of balloon dilation of aortic valve are also good enough for it to be the treatment of choice. Significant lesions of the mitral and tricuspid valve, regurgitant lesions, sub and supra valvular obstructions require surgical correction. Most valvar lesions mandate regular follow up. Communication and coordination between the pediatric cardiologist and the pediatrician helps in the optimal management.


Habitat partitioning among the mayfly species (Ephemeroptera) of Yuccabine Creek, a tropical Australian stream.
This study examines the distributions among microhabitats of 12 detritivorous species of mayfly in Yuccabine Creek, an upland tropical rainforest stream. Analysis of data from regular benthic sampling and from in situ experiments using implanted substrata showed that although all species occurred in all the microhabitats examined, different species had significantly different peaks of abundance in different microhabitats, leading to distinct partitioning of the available habitat. The observed patterns of distribution were closely associated with the distribution of fine detritus deposits (FPOM). In the absence of FPOM in fast-flowing regions of the stream, leaf litter was the prime determinant of species distribution. Current velocity and substratum particle size influenced the distribution of the detritus and leaf litter. Abundance of mayflies was greatest in the pool habitat for all except two of the species.


Effects of radiation and surgery on healing of femoral fractures in a rat model.
Management of soft tissue sarcoma involves multimodality treatment, including surgery and radiotherapy. Pathologic fracture of the femur after such treatment in the thigh is one serious, late complication and nonunion rates of 80-90% are reported. We hypothesize that the combination of radiotherapy and periosteal stripping (during tumor resection) leads to greater impairment of the fracture repair process than either intervention alone. Female Wistar retired breeder rats were randomized into four treatment groups (control, radiotherapy, surgery, and combination of radiotherapy and surgery) and three end-points (21, 28, and 35 days post-fracture). Designated animals first underwent radiotherapy, followed by surgical stripping of the periosteum 3 weeks later and femoral fracture with fixation after another 3 weeks. Animals were sacrificed and fractures examined using microCT and histomorphometry. Simple transverse or short oblique femoral fractures were produced. By 35 days, control animals formed unions, periosteum-stripped animals formed hypertrophic non-unions and irradiated animals formed atrophic non-unions. Histomorphometry revealed an absence of chondroid and osteoid production in animals undergoing radiotherapy. The relative contribution of periosteal stripping to occurrence of non-union was statistically insignificant. Radiation prior to fracture reliably resulted in atrophic non-union in our model. The contribution of periosteal stripping was negligible.


Kinematic analysis of kneeling in cruciate-retaining and posterior-stabilized total knee arthroplasties.
Kneeling is an important function of the knee for many activities of daily living. In this study, we evaluated the in vivo kinematics of kneeling after total knee arthroplasty (TKA) using radiographic based image-matching techniques. Kneeling from 90 to 120 degrees of knee flexion produced a posterior femoral rollback after both cruciate-retaining and posterior-stabilized TKA. It could be assumed that the posterior cruciate ligament and the post-cam mechanism were functioning. The posterior-stabilized TKA design had contact regions located far posterior on the tibial insert in comparison to the cruciate-retaining TKA. Specifically, the lateral femoral condyle in posterior-stabilized TKA translated to the posterior edge of the tibial surface, although there was no finding of subluxation. After posterior-stabilized TKA, the contact position of the post-cam translated to the posterior medial corner of the post with external rotation of the femoral component. Because edge loading can induce accelerated polyethylene wear, the configuration of the post-cam mechanism should be designed to provide a larger contact area when the femoral component rotates.


Alternatives to physician-assisted suicide.
Two alternatives to physician-assisted suicide are ethically supported and legally permitted by American law. They are proper pain management and the forgoing of life-sustaining treatment. Correct understanding of pain management in the context of the dying patient shows that it is always medically possible, and, assuming that the proper decision-maker agrees, it is always legally permitted to eliminate physical pain in an imminently dying patient. It is also ethically right and legal to withhold or withdrew life-sustaining treatment in many cases. These alternatives significantly reduce, though they do not eliminate, the perceived need for suicide and euthanasia. Neither euthanasia nor physician-assisted suicide should be made legal, although they may be morally right in cases in which adequate pain control is unavailable. Reasons for this conclusion are discussed.


Optimization and comparative analysis of LAMP and PCR techniques for the detection of leptospiral DNA in Golden Syrian hamsters.
Leptospirosis is a zoonotic disease with significant public health and economic impact worldwide. Rapid and accurate diagnosis is essential for effective prevention and treatment. This study optimized a loop-mediated isothermal amplification (LAMP) assay using BFo isothermal DNA polymerase with different colorimetric indicators. LAMP was able to detect DNA from pathogenic and intermediate leptospires, while non-pathogenic leptospires and other non-leptospiral microorganisms were negative. LAMP assay combined with calcein showed a tenfold higher limit of detection (1 ng of leptospiral DNA per reaction) than LAMP combined with hydroxynaphthol blue or end-point PCR lipL32 (10 ng of DNA per reaction). Animal samples were collected from infected and non-infected Golden Syrian hamsters (Mesocricetus auratus) to evaluate and compare the performance of LAMP and PCR. These techniques showed a substantial agreement according to Cohen's kappa statistic, being both useful techniques for detecting leptospiral DNA in clinical samples. Overall, this study demonstrates that the LAMP assay is a sensitive, specific, rapid, and simple tool for the detection of leptospiral DNA. It has the potential to facilitate the diagnosis of leptospirosis, particularly in low-income regions with limited diagnosis resources.


B-hematin.
Very rapid production in vitro of a particular type of hematin (B-hematin) with high yield at physiological pH and temperature is presently reported, using a simple chemical system including an organic acid in the absence of any enzyme. B-hematin is characterized by infrared spectra and solubility properties. The antimalarial drug chloroquine practically prevents formation of this hematin under the conditions used. It has recently been suggested that the purified malaria pigment hemozoin is identical with beta-hematin, a form of ferriprotoporphyrin IX sparingly soluble in different solvents which is prepared under non-physiological conditions. Relations between B- and beta-hematin and possible mechanisms of hemozoin formation and antimalarial drug action, are discussed.


Insulin regulates Nedd4-2 via a PKB-dependent mechanism in HEI-OC1 auditory cells-crosstalks with sphingolipid and cAMP signaling.
The mechanisms of association between diabetes and inner ear dysfunction are unknown, although endolymphatic hydrops may be involved. We have previously shown that insulin signaling components are expressed in human saccule and that insulin signaling takes place in HEI-OC1 auditory cells. To explore Nedd4-2 as a target for insulin signaling. Effects of insulin were analyzed using western blot and confocal microscopy in HEI-OC1 auditory cells. Insulin induced phosphorylation of Nedd4-2 and increased the amount of ENaC at the plasma membrane. Also, protein kinase B (PKB) and NDRG1, a substrate for SGK1 (serum and glucocorticoid stimulated kinase), were phosphorylated in response to insulin. The SGK1 inhibitor GSK650394 prevented insulin-induced phosphorylation of NRDG1, but not of PKB and Nedd4-2, whereas the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin and the PKB inhibitor MK2206 inhibited phosphorylation of all components. Ceramides prevented insulin-induced phosphorylation of PKB and NDRG1, but not of Nedd4-2. The ceramide metabolite sphingosine 1-phosphate induced phosphorylation of Nedd4-2. Insulin induces phosphorylation of Nedd4-2, most likely involving PI3K/PKB signaling. Sphingosine 1-phosphate might protect Nedd4-2 against ceramide-induced insulin resistance. Insulin-mediated regulation of Nedd4-2 might impact on inner ear sodium homeostasis with implications for diabetes-induced inner ear damage.


Thirty years of nutrients and biogeochemistry in the Norwegian, Greenland and Iceland Seas, 1990-2019.
This dataset contains biogeochemical samples analyzed by the Plankton Chemistry Laboratory at the Institute of Marine Research (IMR), from the Norwegian, Greenland and Iceland Seas. Number of surveys and stations have varied greatly over the last 3 decades. IMR is conducting one annual Ecosystem Survey in April-May each year, with multiple trawl surveys and net tows, but only CTD water collections are reported here. This month-long exercise also has companion vessels from Iceland and the Faroe Islands surveying their own territorial waters. Three transects are the core of the time-series, visited multiple times each year (Svinøy-NorthWest, Gimsøy-NorthWest, Bjørnøya-West). On each station, the CTD cast is sampled for dissolved inorganic nutrients (nitrate, nitrite, phosphate, silicate) and phytoplankton chlorophyll-a and phaeopigments (ChlA, Phaeo) at predetermined depths. At times, short-term projects have collected samples for Winkler dissolved oxygen titrations (DOW) and particulate organic carbon and nitrogen (POC, PN) determinations. This unique data set has seen limited use over the years but is a great contribution towards global ocean research and climate change investigations.


Xnr2 and Xnr5 unprocessed proteins inhibit Wnt signaling upstream of dishevelled.
Nodal and Nodal-related proteins activate the Activin-like signal pathway and play a key role in the formation of mesoderm and endoderm in vertebrate development. Recent studies have shown additional activities of Nodal-related proteins apart from the canonical Activin-like signal pathway. Here we report a novel function of Nodal-related proteins using cleavage mutants of Xenopus nodal-related genes (cmXnr2 and cmXnr5), which are known to be dominant-negative inhibitors of nodal family signaling. cmXnr2 and cmXnr5 inhibited both BMP signaling and Wnt signaling without activating the Activin-like signal in animal cap assays. Pro region construct of Xnr2 and Xnr5 did not inhibit Xwnt8, and pro/mature region chimera mutant cmActivin-Xnr2 and cmActivin-Xnr5 also did not inhibit Xwnt8 activity. These results indicate that the pro domains of Xnr2 and Xnr5 are necessary, but not sufficient, for Wnt inhibition, by Xnr family proteins. In addition, Western blot analysis and immunohistochemistry analysis revealed that the unprocessed Xnr5 protein is stably produced and secreted as effectively as mature Xnr5 protein, and that the unprocessed Xnr5 protein diffused in the extracellular space. These results suggest that unprocessed Xnr2 and Xnr5 proteins may be involved in inhibiting both BMP and Wnt signaling and are able to be secreted to act on somewhat distant target cells, if these are highly produced.


Rethinking stress resilience.
Resilience to stressful life events has received considerable attention in both clinical and preclinical studies. A number of neural substrates have been identified as putatively mediating resilience to stress. However, there remains considerable diversity in how resilience is defined and studied. This article aims to examine how resilience is defined and conceptualized in social psychology, public health, and related fields, to better inform the understanding of stress resilience in the neurobiological context, and to differentiate resilience from other patterns of response to stressful experiences. An understanding of resilience through the lens of clinical and applied sciences is likely to lead to the identification of more robust and reproducible neural substrates, though many challenges remain.


IFN-γ/TNF-α ratio in response to immuno proteomically identified human T-cell antigens of Mycobacterium tuberculosis - The most suitable surrogate biomarker for latent TB infection.
The enormous reservoir of latent TB infection (LTBI) poses a major hurdle for global TB control. The existing Tuberculin skin test (TST) and IFN-γ release assays (IGRAs) are found to be suboptimal for LTBI diagnosis. Previously we had taken an immunoproteomic approach and identified 10 protein fractions (contains 16 proteins), which are solely recognized by LTBI. In a cohort of 40 pulmonary TB patients (PTB) and 35 healthy household contacts (HHC), IFN-γ and TNF-α response were measured against 16 antigens by using 1:10 diluted whole blood assay. Among all the antigens, IFN-γ response to Rv2626c has shown positivity of 88.57% in HHC and 7.5% in PTB group. IFN-γ response to combination of Rv2626c + Rv3716c has demonstrated 100% positivity in HHC and 17.5% positivity in PTB respectively. Compared to individual cytokines (i.e. IFN-γ and TNF-α), ratio of IFN-γ/TNF-α has shown promising results for diagnosis of LTBI. IFN-γ/TNF-α ratio against Rv3716c and TrxC has exhibited a positivity of 94.29% in HHC and 5% in PTB group. Accession of Rv2626c and Rv3716c may improve the diagnostic performance of existing QFT-GIT. Independent of QFT-GIT assay, ratio of IFN-γ/TNF-α in response to either Rv3716c or TrxC may acts as suitable surrogate biomarker for LTBI.


Proof of concept for identifying cystic fibrosis from perspiration samples.
The gold standard for cystic fibrosis (CF) diagnosis is the determination of chloride concentration in sweat. Current testing methodology takes up to 3 h to complete and has recognized shortcomings on its diagnostic accuracy. We present an alternative method for the identification of CF by combining desorption electrospray ionization mass spectrometry and a machine-learning algorithm based on gradient boosted decision trees to analyze perspiration samples. This process takes as little as 2 min, and we determined its accuracy to be 98 ± 2% by cross-validation on analyzing 277 perspiration samples. With the introduction of statistical bootstrap, our method can provide a confidence estimate of our prediction, which helps diagnosis decision-making. We also identified important peaks by the feature selection algorithm and assigned the chemical structure of the metabolites by high-resolution and/or tandem mass spectrometry. We inspected the correlation between mild and severe CFTR gene mutation types and lipid profiles, suggesting a possible way to realize personalized medicine with this noninvasive, fast, and accurate method.


Pulmonary Nocardiosis Presenting as Exacerbation of Chronic Pulmonary Disease.
Pulmonary nocardiosis (PN) occurs in chronic pulmonary disease (CPD) in the absence of traditional risk factors. Clinical features that differentiate bacterial exacerbations (AE-CPDb) from PN-related exacerbations (AE-CPDPN) are not well described. To describe a series of AE-CPDPN without traditional risk factors and compare clinical features, radiology and outcomes with age, gender and CLD-type matched AE-CPDb. Single-center retrospective review and case-control study. AE-CPDPN had longer duration of symptoms and more leukocytosis at hospitalization. AE-CPDb patients were sicker with more chronic respiratory failure (OR 33.3, p = 0.01), cardiac disease and pulmonary hypertension (OR 6.2, p = 0.008) at diagnosis. More patients with AE-CPDb were discharged on domiciliary oxygen (OR 5.27, p = 0.01). On logistic regression, AE-CPDPN was independently associated with mechanical ventilation (OR 22.3, p = 0.01), length of hospital stay (median difference, 4 days, p = 0.016) but not to hospital mortality. 22.7% of AE-CPDPN died. Respiratory failure requiring oxygen, NIPPV or mechanical ventilation was associated with mortality in AE-CPDPN. PN is a rare cause of AE-CPD and can be suspected by longer symptom duration, more leukocytosis, consolidation and cavitation. AE-CPDPN is associated with longer hospital stay and mechanical ventilation. Respiratory failure is associated with mortality in AE-CPDPN. Pulmonary nocardiosis can present in advanced chronic lung disease as an exacerbation in the absence of traditional risk factors like immunosuppression.Bronchiectasis, followed by chronic obstructive pulmonary disease are the most common chronic lung disease risk factors.Pulmonary nocardiosis is a rare cause of acute exacerbation of chronic pulmonary disease (CPD).Compared to exacerbations of CPD due to bacterial infections, nocardiosis-related exacerbations (CPDPN) were independently related to need for mechanical ventilation and length of hospital stay.Respiratory failure requiring oxygen, noninvasive ventilation and mechanical ventilation are associated with mortality in AE-CPDPN. Kancherla R, Ramanathan RM PL, Appalaraju B, Srinivas R. Pulmonary Nocardiosis Presenting as Exacerbation of Chronic Pulmonary Disease. Indian J Crit Care Med 2019;23(10):467-474.


Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China.
Hepatitis B virus (HBV) infection is a critical global health issue and moderately epidemic in Western China, but HBV molecular epidemiology characteristics are still limited. We conducted this study to investigate HBV genotypes and antiviral resistant mutations in this multi-ethnic area. A total of 1316 HBV patients were recruited from four ethnic groups from 2011 to 2013. Genotypes and resistant mutations were determined by Sanger sequencing. Four genotypes (B, C, D and C/D) were identified. Genotype B and C were common in Han population, while genotype D was predominant in Uygurs. Genotype C was the major genotype in both Tibetans and Yis, and recombinant C/D was found in Tibetans only. Lamivudine resistance was common in all populations, especially in Hans with prevalence of 42.8%. Entecavir resistance was barely observed regardless of ethnicity. Genotype C isolates had higher rates of rtA181T/V than genotype B (13.5% vs. 5.1%, P < 0.001), in accordance with higher prevalence of resistance to adefovir (20.0% vs. 9.5%, P < 0.001). While incidence of resistant mutations to other drugs and clinical factors showed no difference among different genotypes. HBV genotypes and resistance-conferring mutations had different geographic and demographic distributions in Western China, which provided molecular epidemiology data for clinical management.


Self-assembly pathways in a triphenylalanine peptide capped with aromatic groups.
Peptide derivatives and, most specifically, their self-assembled supramolecular structures are being considered in the design of novel biofunctional materials. Although the self-assembly of triphenylalanine homopeptides has been found to be more versatile than that of homopeptides containing an even number of residues (i.e. diphenylalanine and tetraphenylalanine), only uncapped triphenylalanine (FFF) and a highly aromatic analog blocked at both the N- and C-termini with fluorenyl-containing groups (Fmoc-FFF-OFm), have been deeply studied before. In this work, we have examined the self-assembly of a triphenylalanine derivative bearing 9-fluorenylmethyloxycarbonyl and benzyl ester end-capping groups at the N- and C-termini, respectively (Fmoc-FFF-OBzl). The antiparallel arrangement clearly dominates in β-sheets formed by Fmoc-FFF-OBzl, whereas the parallel and antiparallel dispositions are almost isoenergetic in Fmoc-FFF-OFm β-sheets and the parallel one is slightly favored for FFF. The effects of both the peptide concentration and the medium on the self-assembly process have been examined considering Fmoc-FFF-OBzl solutions in a wide variety of solvent:co-solvent mixtures. In addition, Fmoc-FFF-OBzl supramolecular structures have been compared to those obtained for FFF and Fmoc-FFF-OFm under identical experimental conditions. The strength of π-π stacking interactions involving the end-capping groups plays a crucial role in the nucleation and growth of supramolecular structures, which determines the resulting morphology. Finally, the influence of a non-invasive external stimulus, ultrasounds, on the nucleation and growth of supramolecular structures has been examined. Overall, FFF-based peptides provide a wide range of supramolecular structures that can be of interest in the biotechnological field.


Phenotypic and genomic characteristics of Brevibacterium zhoupengii sp. nov., a novel halotolerant actinomycete isolated from bat feces.
Two strictly aerobic, Gram-staining-positive, non-spore-forming, regular rod-shaped (approximately 0.7 × 1.9 mm) bacteria (HY170T and HY001) were isolated from bat feces collected from Chongzuo city, Guangxi province (22°20'54″N, 106°49'20″E, July 2011) and Chuxiong Yi Autonomous Prefecture, Yunnan province (25°09'10″N, 102°04'39″E, October 2013) of South China, respectively. Optimal growth is obtained at 25-28°C (range, 4-32°C) on BHI-5% sheep blood plate with pH 7.5 (range, 5.0-10.0) in the presence of 0.5-1.0% NaCl (w/v) (range, 0-15% NaCl [w/v]). The phylogenetic and phylogenomic trees based respectively on the 16S rRNA gene and 845 core gene sequences revealed that the two strains formed a distinct lineage within the genus Brevibacterium, most closely related to B. aurantiacum NCDO 739T (16S rRNA similarity, both 98.5%; dDDH, 46.7-46.8%; ANI, 91.9-92.1%). Strain HY170T contained MK-8(H2), diphosphatidylglycerol (DPG) and phosphatidylglycerol (PG), galactose and ribose as the predominant menaquinone, major polar lipids, and main sugars in the cell wall teichoic acids, respectively. The meso-diaminopimelic acid (meso-DAP) was the diagnostic diamino acid of the peptidoglycan found in strain HY170T. Anteiso-C15:0 and anteiso-C17:0 were the major fatty acids (> 10%) of strains HY170T and HY001, with anteiso-C17:1A predominant in strain HY170T but absent in strain HY001. Mining the genomes revealed the presence of secondary metabolite biosynthesis gene clusters encoding for non-alpha poly-amino acids (NAPAA), ectoine, siderophore, and terpene. Based on results from the phylogenetic, chemotaxonomic and phenotypic analyses, the two strains could be classified as a novel species of the genus Brevibacterium, for which the name Brevibacterium zhoupengii sp. nov. is proposed (type strain HY170T = CGMCC 1.18600T = JCM 34230T).


Identification of Key Drug Targets and Molecular Mechanisms of Curcumae Rhizoma Acting on HBV-Related HCC: Weighted Correlation Network and Network Pharmacological Analyses.
Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has poor prognosis and high mortality rate. Curcumae Rhizoma, a classic Chinese medicinal herb, is often used to treat tumors. Active ingredients of Curcumae Rhizoma were extracted from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database, and potential targets were predicted by the TCMSP database and Swiss Target Prediction database. The key drug targets were filtered by intersecting predicted targets, DEGs, and genes in important modules from WGCNA. Besides, the key drug targets were used to construct a network of "herb-active ingredient-target-disease" interactions and subjected to enrichment analysis and protein-protein interaction (PPI) analysis. The hub targets based on PPI analysis was evaluated by the KMplotter database. Three active ingredients of Curcumae Rhizoma were collected with OB ≥ 30% and DL ≥ 0.18, including hederagenin, wenjine, and bisdemethoxycurcumin. The key drug targets were mainly enriched in cell cycle checkpoint, DNA integrity checkpoint, and peptidyl-serine modification. Besides, Curcumae Rhizoma treatment of HBV-related HCC mainly involved the p53 signaling pathway and arachidonic acid metabolism. Finally, ESR1 and PTGS2 were identified as hub targets from PPI analysis. ESR1 was found to be correlated with survival in liver cancer patients with hepatitis. Based on WGCNA and network pharmacological analysis, our results illustrated that Curcumae Rhizoma might work through regulating multitargets and multipathways in HBV-related HCC.


Activity-Based Protein Profiling at the Host-Pathogen Interface.
Activity-based protein profiling (ABPP) is a technique for selectively detecting reactive amino acids in complex proteomes with the aid of chemical probes. Using probes that target catalytically active enzymes, ABPP can rapidly define the functional proteome of a biological system. In recent years, this approach has been increasingly applied to globally profile enzymes active at the host-pathogen interface of microbial infections. From in vitro co-culture systems to animal models of infection, these studies have revealed enzyme-mediated mechanisms of microbial pathogenicity, host immunity, and metabolic adaptation that dynamically shape pathogen interactions with the host.


The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers.
Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Only MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers.


Synthesis of the vancomycin CDE ring system.
A first generation synthesis of 22 is described constituting the first disclosure of the preparation of an appropriately protected and fully functionalized vancomycin CDE ring system complete with the C and E ring monochloro substitution pattern. The approach, which is based on two aromatic nucleophilic substitution reactions for sequential CD and DE macrocyclization, provided the opportunity to define and indirect solution to the control of the CDE atropisomer stereochemistry through selective thermal equilibration of the DE versus unaltered CD ring system. Its success provides a rationale for a preferred order to the CD and DE ring system introductions.


Advances in intelligent DNA nanomachines for targeted cancer therapy.
As an emerging field, DNA nanotechnology has been applied to the fabrication of drug delivery systems. Unprecedented spatial addressability and intrinsic sequence encoding enable DNA strands to self-assemble into well-defined 2D and 3D DNA nanostructures with specifically controlled sizes, shapes and surface charges. Multifunctional DNA nanostructures have been created and applied as promising platforms for drug delivery, imaging, and theranostics. Advantages of chemotherapy, gene therapy, and immunotherapy, among others, have been integrated into such functional nanodevices, showing potential in tumor-targeted therapy and diagnosis. In this review, we summarize general methods for the construction of DNA nanodevices and focus on targeting strategies favored by the compatibility of DNA nanotechnology. Additionally, we highlight the outlook and challenges facing the use of DNA nanotechnology in cancer therapy.


Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: an open-label, non-inferiority, randomised trial.
Yaws--an endemic treponematosis and, as such, a neglected tropical disease--is re-emerging in children in rural, tropical areas. Oral azithromycin is effective for syphilis. We assessed the efficacy of azithromycin compared with intramuscular long-acting penicillin to treat patients with yaws. We did an open-label, non-inferiority, randomised trial at Lihir Medical Centre, Papua New Guinea, between Sept 1, 2010, and Feb 1, 2011. Children aged 6 months to 15 years with a serologically confirmed diagnosis of yaws were randomly allocated, by a computer-generated randomisation sequence, to receive either one 30 mg/kg oral dose of azithromycin or an intramuscular injection of 50,000 units per kg benzathine benzylpenicillin. Investigators were masked to group assignment. The primary endpoint was treatment efficacy, with cure rate defined serologically as a decrease in rapid plasma reagin titre of at least two dilutions by 6 months after treatment, and, in participants with primary ulcers, also by epithelialisation of lesions within 2 weeks. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10%. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01382004. We allocated 124 patients to the azithromycin group and 126 to the benzathine benzylpenicillin group. In the per-protocol analysis, after 6 months of follow-up, 106 (96%) of 110 patients in the azithromycin group were cured, compared with 105 (93%) of 113 in the benzathine benzylpenicillin group (treatment difference -3·4%; 95% CI -9·3 to 2·4), thus meeting prespecified criteria for non-inferiority. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (ten [8%] in the azithromycin group vs eight [7%] in the benzathine benzylpenicillin group). A single oral dose of azithromycin is non-inferior to benzathine benzylpenicillin and avoids the need for injection equipment and medically trained personnel. A change to the simpler azithromycin treatment regimen could enable yaws elimination through mass drug administration programmes. International SOS and Newcrest Mining.


Effect of labor on postpartum clearance of cell-free fetal DNA from the maternal circulation.
The aim of this study was to compare the effect of mode of delivery on the postpartum clearance of cell-free fetal (cff) DNA. Women who gave birth to a single-term male infant by any mode of delivery had blood collected on three occasions: within 3 h of birth, on day 1-2 postpartum and at 2 weeks postpartum. The SRY sequence was used as a marker of cff DNA, and was detected using conventional PCR. Eighty-seven women were included in the study. There were 28 women in the elective caesarean section group and 59 in the labor group. Cell-free fetal DNA was detected in 38/87 (44%) of women within 3 h of birth. There was a significant difference between the group that labored and the group that did not (54 vs 21%, p = 0.003). Twelve percent of women who labored had persistent cff DNA on day 1-2 postpartum, compared with none of the women who delivered without labor. No woman had DNA that persisted up to 2 weeks postpartum. The presence of labor increases the rate of detectable DNA in women within 3 h of birth and on day 1-2 postpartum. Postpartum clearance was completed by 2 weeks in all women tested regardless of mode of delivery.


Detection of the viral sarcoma gene product in cells infected with various strains of avian sarcoma virus and of a related protein in uninfected chicken cells.
Genetic analyses have defined a single gene (src) as that portion of the avian sarcoma virus (ASV) genome which encodes the protein directly responsible for ASV-induced neoplastic transformation. We have recently identified the polypeptide product of the src gene of the Schmidt-Ruppin (SR) strain of ASV, a 60,000-dalton phosphoprotein designated pp60(src), and have further determined that pp60(src) acts as a protein kinase. Essential to the identification and characterization of the pp60(src) protein of SR-ASV was the use of serum (TBR serum) from rabbits bearing SR-ASV-induced tumors. TBR serum was, however, strain specific, recognizing pp60(src) from SR-ASV-transformed cells only. We report here that sera from marmosets bearing tumors induced by the Bryan or SR strains of ASV (TBM sera) contain antibody which precipitates the transforming gene product from cells transformed by the SR, Bryan, Prague, or Bratislava strains of ASV. In contrast, rabbits bearing tumors induced by either the Bratislava or Bryan strains of ASV, or hamsters with SR-ASV-induced tumors did not produce antibody to pp60(src) from any strain of ASV. The 60,000-dalton polypeptides immunoprecipitated with TBM serum from cells transformed by each of the above virus strains are phosphoproteins. One-dimensional peptide mapping by limited proteolysis revealed that the pp60(src) proteins are structurally very similar, but not identical. Furthermore, all of the viral pp60(src) proteins have an associated phosphotransferase activity. In addition to detecting the viral src proteins, TBM serum was able to immunoprecipitate an antigenically related protein from normal uninfected avian cells.


[Dapsone for chronic skin lesions in 3 children suffering from Henoch-Schönlein vasculitis].
We describe 3 cases of chronic purpuric skin lesions in children suffering from systemic vasculitis: 3 children with Henoch-Schönlein purpura. Dapsone was introduced when skin lesions were recurrent, extensive, and persistent, due to its known ability to act as an anti-IgA and as an anticytotoxic agent against polynuclear neutrophils. Fast and complete but purely suspensive healing of skin lesions was noted. One child developed methemoglobinemia, a known side-effect of dapsone, highlighting the need for adequate prescription and follow-up.


Helicobacter pylori and perforated peptic ulcer prevalence of the infection and role of non-steroidal anti-inflammatory drugs.
To study the prevalence of Helicobacter pylori infection in patients with perforated peptic ulcer, to compare it with the prevalence in patients with uncomplicated ulcer, and to assess the role of non-steroidal anti-inflammatory drugs in this prevalence. Consecutive patients with perforated peptic ulcer were included in this retrospective study. As a control group, patients undergoing elective outpatient evaluation for the investigation of dyspepsia during the same time period and found to have a peptic ulcer at endoscopy were included. A 13C-urea breath test was carried out in all patients to diagnose H. pylori infection. Sixteen patients with perforated peptic ulcer and 160 with non-complicated peptic ulcer were included. Sixty-two percent of the patients with perforated peptic ulcer were infected by H. pylori, while the microorganism was detected in 87% of the patients without this complication (P = 0.01). Non-steroidal anti-inflammatory drugs intake was more frequent (P = 0.012) in patients with perforated peptic ulcers (56%) than in those without perforation (26%). H. pylori prevalence in perforated peptic ulcers was of 44% in patients with non-steroidal anti-inflammatory drugs intake, but this figure increased up to 86% when only patients not taking non-steroidal anti-inflammatory drugs were considered (P = 0.09). In the multivariate analysis, non-steroidal anti-inflammatory drugs intake was the only variable that correlated with peptic ulcer perforation [odds ratio, 3.6 (95% confidence interval, 1.3-10); P = 0.016]. The mean prevalence of H. pylori infection in patients with perforated peptic ulcer is, overall, of only about 60%, which contrasts with the 90-100% figure usually reported in non-complicated ulcer disease. However, the most important factor associated with H. pylori-negative perforated peptic ulcer is non-steroidal anti-inflammatory drugs use, and if this factor is excluded, prevalence of infection is almost 90%, similar to that found in patients with non-perforating ulcer disease.


Surgical management of cervical carcinoma.
Surgical management for cervical carcinoma uses a wide variety of procedures for all stages of disease, ranging from the most conservative excisional biopsy to aggressive extirpative surgery with sophisticated reconstruction. Innovative surgical procedures have given fertility-sparing treatment options to women of reproductive age, and refinement and use of minimally invasive surgical approaches have minimized operative morbidity without sacrificing outcomes. Conservative staging procedures are being evaluated to improve survival in locally advanced disease. There have been many breakthroughs in the treatment of cervical carcinoma over recent years, which have improved not only survival but also the quality of ensuing life for women afflicted by this disease.


Intracoronary artery retrograde thrombolysis for ST-segment elevation myocardial infarction with a tortuous coronary artery: A case report and review of the literature.
How to deal with large thrombus burdens of culprit's blood vessel remains a great challenge in the treatment of acute myocardial infarction. A 32-year-old Chinese man was diagnosed with ST-segment elevation myocardial infarction (STEMI). Coronary angiography revealed that the distal end of a tortuous left circumflex was completely occluded by a large amount of thrombus. Cutted balloon-directed intracoronary artery retrograde thrombolysis (ICART) with urokinase led to the restoration of coronary blood flow. Because there was no obvious plaque rupture or artery stenosis in the coronary artery, it was only dilated, and no stent was implanted. Cutted balloon-directed ICART can be performed effectively and safely in some STEMI patients with tortuous coronary vessels and large thrombus. (REST or named ICART ClinicalTrials.gov number, ChiCTR1900023849).


[Isolated left ventricular non-compaction: a single-center experience].
Isolated left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by excessive and prominent trabeculations associated with deep recesses that communicate with the ventricular cavity. Determining the natural history of this condition has been hampered by differences in clinical features and prognosis in published series, which are partly the result of differing diagnostic criteria and the lack of management guidelines. This work aims to contribute to the characterization of isolated LVNC by analyzing an affected population in terms of clinical presentation, diagnosis, risk stratification, treatment and follow-up. We also discuss the most relevant data from the literature concerning this cardiomyopathy.


Does the reuse of PET bottles during solar water disinfection pose a health risk due to the migration of plasticisers and other chemicals into the water?
Solar water disinfection (SODIS) is a simple, effective and inexpensive water treatment procedure suitable for application in developing countries. Microbially contaminated water is filled into transparent polyethylene terephthalate (PET) plastic bottles and exposed to full sunlight for at least 6h. Solar radiation and elevated temperature destroy pathogenic germs efficiently. Recently, concerns have been raised insinuating a health risk by chemicals released from the bottle material polyethylene terephthalate (PET). Whereas the safety of PET for food packaging has been assessed in detail, similar investigations for PET bottles used under conditions of the SODIS treatment were lacking until now. In the present study, the transfer of organic substances from PET to water was investigated under SODIS conditions using used colourless transparent beverage bottles of different origin. The bottles were exposed to sunlight for 17h at a geographical latitude of 47 degrees N. In a general screening of SODIS treated water, only food flavour constituents of previous bottle contents could be identified above a detection limit of 1 microg/L. Quantitative determination of plasticisers di(2-ethylhexyl)adipate (DEHA) and di(2-ethylhexyl)phthalate (DEHP) revealed maximum concentrations of 0.046 and 0.71 microg/L, respectively, being in the same range as levels of these plasticisers reported in studies on commercial bottled water. Generally, only minor differences in plasticiser concentrations could be observed in different experimental setups. The most decisive factor was the country of origin of bottles, while the impact of storage conditions (sunlight exposure and temperature) was less distinct. Toxicological risk assessment of maximum concentrations revealed a minimum safety factor of 8.5 and a negligible carcinogenic risk of 2.8 x 10(-7) for the more critical DEHP. This data demonstrate that the SODIS procedure is safe with respect to human exposure to DEHA and DEHP.


Defining Endothelial Cell-Derived Factors That Promote Pericyte Recruitment and Capillary Network Assembly.
We sought to identify and investigate the functional role of the major endothelial cell (EC)-derived factors that control pericyte recruitment to EC tubes and pericyte-induced tube maturation during capillary network formation. Approach and Results: We identify PDGF (platelet-derived growth factor)-BB, PDGF-DD, ET (endothelin)-1, TGF (transforming growth factor)-β, and HB-EGF (heparin-binding epidermal growth factor), as the key individual and combined regulators of pericyte assembly around EC tubes. Using novel pericyte only assays, we demonstrate that PDGF-BB, PDGF-DD, and ET-1 are the primary direct drivers of pericyte invasion. Their addition to pericytes induces invasion as if ECs were present. In contrast, TGF-β and HB-EGF have minimal ability to directly stimulate pericyte invasion. In contrast, TGF-β1 can act as an upstream pericyte primer to stimulate invasion in response to PDGFs and ET-1. HB-EGF stimulates pericyte proliferation along with PDGFs and ET-1. Using EC-pericyte cocultures, individual, or combined blockade of these EC-derived factors, or their pericyte receptors, using neutralizing antibodies or chemical inhibitors, respectively, interferes with pericyte recruitment and proliferation. As individual factors, PDGF-BB and ET-1 have the strongest impact on these events. However, when the blocking reagents are combined to interfere with each of the above factors or their receptors, more dramatic and profound blockade of pericyte recruitment, proliferation, and pericyte-induced basement membrane deposition occurs. Under these conditions, ECs form tubes that become much wider and less elongated as if pericytes were absent. Overall, these new studies define and characterize a functional role for key EC-derived factors controlling pericyte recruitment, proliferation, and pericyte-induced basement membrane deposition during capillary network assembly.


Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis.
In cystic fibrosis (CF), Pseudomonas aeruginosa undergoes intra-strain genotypic and phenotypic diversification while establishing and maintaining chronic lung infections. As the clinical significance of these changes is uncertain, we investigated intra-strain diversity in commonly shared strains from CF patients to determine if specific gene mutations were associated with increased antibiotic resistance and worse clinical outcomes. Two-hundred-and-one P. aeruginosa isolates (163 represented a dominant Australian shared strain, AUST-02) from two Queensland CF centres over two distinct time-periods (2001-2002 and 2007-2009) underwent mexZ and lasR sequencing. Broth microdilution antibiotic susceptibility testing in a subset of isolates was also performed. We identified a novel AUST-02 subtype (M3L7) in adults attending a single Queensland CF centre. This M3L7 subtype was multi-drug resistant and had significantly higher antibiotic minimum inhibitory concentrations than other AUST-02 subtypes. Prospective molecular surveillance using polymerase chain reaction assays determined the prevalence of the 'M3L7' subtype at this centre during 2007-2009 (170 patients) and 2011 (173 patients). Three-year clinical outcomes of patients harbouring different strains and subtypes were compared. MexZ and LasR sequences from AUST-02 isolates were more likely in 2007-2009 than 2001-2002 to exhibit mutations (mexZ: odds ratio (OR) = 3.8; 95% confidence interval (CI): 1.1-13.5 and LasR: OR = 2.5; 95%CI: 1.3-5.0). Surveillance at the adult centre in 2007-2009 identified M3L7 in 28/509 (5.5%) P. aeruginosa isolates from 13/170 (7.6%) patients. A repeat survey in 2011 identified M3L7 in 21/519 (4.0%) P. aeruginosa isolates from 11/173 (6.4%) patients. The M3L7 subtype was associated with greater intravenous antibiotic and hospitalisation requirements, and a higher 3-year risk of death/lung transplantation, than other AUST-02 subtypes (adjusted hazard ratio [HR] = 9.4; 95%CI: 2.2-39.2) and non-AUST-02 strains (adjusted HR = 4.8; 95%CI: 1.4-16.2). This suggests ongoing microevolution of the shared CF strain, AUST-02, was associated with an emerging multi-drug resistant subtype and possibly poorer clinical outcomes.


US initiative for prediabetes.
Health officials in the USA want physicians to help to reduce diabetes by asking at-risk patients to join diabetes prevention programmes. Susan Jaffe reports from Washington, DC.


[Strength, flexibility, balance, resistance and flexibility assessment according to body mass index in active older women].
Overweight and obesity are increasing at an alarming rate among older people. This is mainly because this population is predominantly sedentary. The aim of this study was to classify, according to the body mass index (BMI), a group of older active women and to evaluate the different basic physical abilities as a function of this. The BMI and fitness were evaluated in 60 elderly active women (mean age: 66.14 ± 6.59 years) using the 2-minute step test, arm curl test, chair stand test, back scratch test, chair-sit and reach-test, flamenco test, and 8-foot up-and-go test. It was found that 52.23% of the women studied had a normal BMI and 47.76% were slightly overweight. There were no cases of obesity or underweight. Women with normal BMI had better values in all tests than overweight women. Significant differences were found in the flamenco test (P<.05), and 8-foot up-and-go test (P<.01). Older women who usually do physical activity had a normal or slightly overweight BMI. It was also found that women with lower BMI have better resistance, flexibility, balance and strength.


Is Surgery the Only Fate of the Patient with Leriche Syndrome? Our Endovascular Therapy Results Early Follow-Up Outcomes.
In this research, we aimed to present early follow-up results of the endovascular treatment in patients with Leriche syndrome at our single center. Between October 2020 and January 2022, 14 patients with Leriche syndrome (12 men, two women) who underwent endovascular treatment at our center retrospectively were evaluated. Before the treatment, the ankle-brachial index (ABI) was found 0.50 ± 0.11 on the right leg and 0.45 ± 0.09 on the left leg. All of the patients with Leriche syndrome applied to our clinic for the first time. In five patients, the fully occluded lesion length was over 3 cm (ranging between 3.5-7.2 cm), hence they were treated with aortic and bilateral iliac bare metallic stents. Although in one patient, the aortic occluding lesion was below 3 cm; it was treated with a bare aortic and bilateral bare iliac stent application because the lesion in the aorta was too calcific. In eight patients, the lesion length was less than 3 cm, bilateral iliac metal bare stents were applied in a kissing stent way. Endovascular therapy for chronic aorto-iliac occlusive disease has an early high technical success with primary and secondary patency rates. Especially in patients with high risk factors, it may be considered as a good alternative to conventional surgery.


Relationship between diverse patient body size- and image acquisition-related factors, and quantitative and qualitative image quality in coronary computed tomography angiography: a multicenter observational study.
We investigated the effects of patient- and image acquisition-related factors on the image quality in coronary CT angiography (CCTA). We enrolled 1197 patients (728 men; 65 ± 12 years). All underwent CCTA under the routine scan protocol in 23 participating hospitals. The subjective image quality (3-point Likert scale: excellent, good, and poor) and the attenuation of the left and right coronary artery (LCA, RCA) were recorded; the effects of patient and image acquisition-related factors on vascular attenuation were then compared. The mean LCA attenuation was 515.2 ± 65.8 (excellent), 401.4 ± 63.4 (good), and 319.5 ± 47.6 HU (poor). The corresponding RCA attenuation was 496.6 ± 67.6, 390.5 ± 58.5, and 308.5 ± 50.7 HU, respectively. Univariate analysis revealed significant associations between sufficient coronary attenuation (> 400 HU) and the age, gender, body surface area (BSA), number of detectors, contrast synchronization, scan mode, and the fractional contrast dose. Multivariate analysis revealed that the bolus tracking method, prospective electrocardiogram gating, and fractional contrast dose were significantly associated with sufficient coronary enhancement. BSA and fractional contrast dose are the most important patient- and image acquisition-related factors for sufficient coronary attenuation in CCTA.


FM 100 Hue test and lightness discrimination test.
Some practical tips are given. With the help of the caps of the FM 100 Hue test simpler tests can be made, such as a Panel D-15 test. If 16 additional grey caps are procured the light sensitivity can also be determined. The durability of a colour specimen is doubled if a ring is fitted into the cap.


Identification of 7xi-hydroxytetrahydrocortisol and 7xi-hydroxytetrahydrocortisone from urine of newborn baboons (Papio papio).
Two highly polar, unconjugated metabolltes of tetrahydrocortisol and tetrahydrocortisone, which had been shown previously to account for greater than 40% of [14C]cortisol (F) administered to baboon neonates, were isolated from urine of a term newborn animal. Metabolites were extracted with ethyl acetate, purified by sequential paper chromatography and crystallization, and identified by chemical and biochemical procedures. Both metabolites of F are 5beta-pregnanes with a hydroxyl of unknown orientation at C-7, a 3alpha-hydroxyl, and a dihydroxyacetone side chain. The two compounds differ from each other by the presence of either oxo or hydroxyl functions at C-11. The following nomenclature is proposed: unknown 1: 3alpha,7xi,11beta,17,21-pentahydroxy-5beta-pregnan-20-one (7xi-hydroxytetrahydrocortisol); unknown 11: 3alpha,7xi,17,21-tetrahydroxy-5beta-pregnane-11,20-dione (7xi-hydroxytetrahydrocortisone). Production of these compounds compensates quantitatively for the decreased formation of F glucuronoside metabolites by baboon neonates, compared with that in adults. Therefore, we propose that 7-hydroxylation is a major alternative pathway for F metabolism in the perinatal period of the baboon.


Development and application of proteomics technologies in Saccharomyces cerevisiae.
Proteomics research focuses on the identification and quantification of "all" proteins present in cells, organisms or tissue. Proteomics is technically complicated because it encompasses the characterization and functional analysis of all proteins that are expressed by a genome. Moreover, because the expression levels of proteins strongly depend on complex regulatory systems, the proteome is highly dynamic. This review focuses on the two major proteomics methodologies, one based on 2D gel electrophoresis and the other based on liquid chromatography coupled to mass spectrometry. The recent developments of these methodologies and their application to quantitative proteomics are described. The model system Saccharomyces cerevisiae is considered to be the optimal vehicle for proteomics and we review studies investigating yeast adaptation to changes in (nutritional) environment.


Photosynthesis and water relations and the role of anatomy in Umbilicariaceae (lichenes) from Central Spain.
The response of net photosynthesis and dark respiration in eight species of Umbilicariaceae (lichenes) to temperature (-5, 0, 5, 10, 15, 20, 25, 30°C) and irradiance (55, 110, 220, 400, 620 μmol photons m-2 s-1 PAR) was studied. The samples were collected in montane and alpine localities of the Spanish Sistema Central. The species differed widely in their net photosynthetic rates. The optimal temperature for net photosynthesis in alpine species was significantly lower than in montane species. Montane species were more photophytic than alpine ones. Water saturation and water loss rate were dependent on morphology and particularly anatomy of the thallus. The physiological and structural data are useful in the interpretation of the ecology and altitudinal distribution of the Umbilicariaceae. No adaptation could be linked to particularities of the mediterranean climate.


A mock circulation loop to test extracorporeal CO2 elimination setups.
Extracorporeal carbon dioxide removal (ECCO2R) is a promising yet limited researched therapy for hypercapnic respiratory failure in acute respiratory distress syndrome and exacerbated chronic obstructive pulmonary disease. Herein, we describe a new mock circuit that enables experimental ECCO2R research without animal models. In a second step, we use this model to investigate three experimental scenarios of ECCO2R: (I) the influence of hemoglobin concentration on CO2 removal. (II) a potentially portable ECCO2R that uses air instead of oxygen, (III) a low-flow ECCO2R that achieves effective CO2 clearance by recirculation and acidification of the limited blood volume of a small dual lumen cannula (such as a dialysis catheter). With the presented ECCO2R mock, CO2 removal rates comparable to previous studies were obtained. The mock works with either fresh porcine blood or diluted expired human packed red blood cells. However, fresh porcine blood was preferred because of better handling and availability. In the second step of this work, hemoglobin concentration was identified as an important factor for CO2 removal. In the second scenario, an air-driven ECCO2R setup showed only a slightly lower CO2 wash-out than the same setup with pure oxygen as sweep gas. In the last scenario, the low-flow ECCO2R, the blood flow at the test membrane lung was successfully raised with a recirculation channel without the need to increase cannula flow. Low recirculation ratios resulted in increased efficiency, while high recirculation ratios caused slightly reduced CO2 removal rates. Acidification of the CO2 depleted blood in the recirculation channel caused an increase in CO2 removal rate. We demonstrate a simple and cost effective, yet powerful, "in-vitro" ECCO2R model that can be used as an alternative to animal experiments for many research scenarios. Moreover, in our approach parameters such as hemoglobin level can be modified more easily than in animal models.


In vivo inhibition of epidermal growth factor receptor autophosphorylation prevents receptor internalization.
The question whether epidermal growth factor (EGF)-induced receptor endocytosis requires the prior autophosphorylation via the EGF receptor (EGFR) kinase domain has been a matter of long-standing debate. In the airway epithelial cell line NCI-H292, the EGFR kinase domain inhibitor BIBW 2948 BS was found to inhibit both autophosphorylation and subsequent internalization of the endogenous EGFR with similar IC₅₀ values. Applying an ex vivo EGFR internalization assay in a clinical study, the in vivo effect of inhalatively administered BIBW 2948 BS was determined directly at the targeted receptor in airway tissues from COPD patients. In these experiments, the in vivo inhibition of the EGFR kinase domain prevented the EGF-induced internalization of EGFR.


Time-resolved fluorescence study during denaturation and renaturation of curcumin-myoglobin complex.
Curcumin influences the transition point, the concentration of denaturant required to effect 50% of the total change, of myoglobin denaturation. Curcumin enhances absorbance of myoglobin at 280 nm with a binding constant K=3.0×10(4) M(-1) whereas fluorescence of curcumin is quenched by myoglobin with a Stern-Volmer association constant of 2.5×10(5) M(-1). Unfolding process of myoglobin-curcumin induces a recovery in fluorescence lifetime loss. The gain in time-resolved fluorescence lifetime during unfolding has been again lost during refolding of curcumin-myoglobin complex by dilution process suggesting partial reversibility of unfolding process for both myoglobin and curcumin-myoglobin complex.


Facile construction of cost-effective zinc-aluminium polymeric framework for efficient removal of selective both drug and dye from an aqueous medium.
A novel aluminium (Al) and its active alloys are extensively been used in nearly all areas owing to their cost-effectiveness. But when it is subjected to an aqueous medium, gets corroded through a chemical response. In this paper, a novel framework was fabricated by copolymer coating over on Al and loaded with zinc via electro polymerization and electrodeposition method ([EDA- OPDA]Al@Zn). The as-fabricated composite has emerged for the sorption of Methylene Blue (MB) aqueous dye and Paracetomal drug (PAR). The as-fabricated composite framework has been categorized via IR spectra, FE-SEM images, and EDX spectra. The sorption progression was optimized for numerous prompting features like pH, contact time and impact of dosage. Based on kinetics data, the growth in QE value by an enhancement in temperature for adsorption and the higher r values shows the adsorption progression is a pseudo-second-order model. The thermodynamic constraints specify that the field of adsorbate is impulsive and typical endothermic process. Instead, the corrosion resistance of a composite in the 3.5% of NaCl. Solution was explored via EIS spectra and potentio-dynamic polarization. Depending on the observed features, it indicates that the [EDA-OPDA]Al@Zn framework provided fantastic corrosion resistance. So it is obvious that the as-synthesized framework is of multitasking, that it could be successfully performed for the exclusion of MB aqueous dye and PAR drug from the aqueous medium and it also withstands effectively in this corrosive medium.


Prevalence of plasma small dense LDL is increased in obesity in a Thai population.
Plasma low density lipoprotein (LDL) particles vary in size, density, electrical charge and chemical composition. An increased presence of small dense LDL (sdLDL), along with raised triglyceride concentrations and decreased high density lipoprotein (HDL) cholesterol concentrations is commonly known as the atherogenic triad and has been observed in some cases of obesity, principally in Europe and America. This study examines the prevalence of sdLDL in the plasma of an obese (BMI≥25 kg/m2) Thai population. Plasma from fasted obese (n=48) and non-obese (n=16) Thai participants was subjected to density gradient ultracentrifugation in iodixanol to separate lipoproteins. Gradients were unloaded top-to-bottom into 20 fractions which were assayed for cholesterol, triglyceride, apo B and apo A-1 to identify lipoprotein types and subtypes. LDL cholesterol was subfractionated into LDL I+II (fractions 3-6, ρ=1.021-1.033 g/ml) which was considered to represent large buoyant LDL (lbLDL), LDL III (fractions 7-9, ρ=1.036-1.039 g/ml) which was considered to represent sdLDL, and, LDL IV (fractions 10-12, ρ=1.044-1.051 g/ml) which was considered to represent very sdLDL. Concentrations of LDL III and IV were increased by 15-20% in obese participants whilst that of LDL I+II was concomitantly decreased by 10%. This was accompanied by a 50% increase in plasma triglyceride concentrations and 15% decrease in HDL cholesterol concentrations. Only 3/16 (19%) non-obese participants had a pattern B LDL cholesterol profile (peak density of >1.033 g/ml), whilst 28/48 (58%) obese participants were pattern B. When expressed as a fraction of the LDL concentration, total sdLDL (i.e. LDL III+IV) showed highly significant correlations to plasma triglyceride concentrations and the triglyceride/HDL cholesterol ratio. The prevalence of sdLDL is increased in obesity in a Thai population such that they demonstrate a similar atherogenic triad to that previously observed in European and American populations.


Moderators and predictors of response to deep transcranial magnetic stimulation for obsessive-compulsive disorder.
Deep transcranial magnetic stimulation (dTMS) has emerged as a treatment option for adults with obsessive-compulsive disorder (OCD) who continue to exhibit impairing symptoms following an adequate response to first line interventions. Currently, little is known about the predictors or moderators of dTMS outcome for OCD. This paper examined if several theoretically relevant variables may predict and moderate treatment effects including OCD symptom severity, functional impairment, co-occurring depressive symptoms, age, gender, age of OCD onset, and family history of OCD. As part of a previously reported study, 100 patients received 29 dTMS or sham stimulation treatments over 6 weeks. dTMS was administered using a Magstim Rapid2 TMS (The Magstim Co. Ltd., Whitland, Carmarthenshire, United Kingdom) stimulator equipped with a H shaped coil design, which was specifically designed to stimulate the dorsal mPFC-ACC bilaterally. Findings suggest older participants and those with lower OCD severity and disability respond faster to both dTMS and sham stimulation. dTMS of the dorsal mPFC/ACC appeared to have larger benefits for individuals with greater OCD severity, whereas the difference between treatment arms was minimal in those with lower severity. Implications of these findings for treatment of OCD are discussed.


Does plasma HDL-C concentration interact with whole-body cholesterol metabolism?
This review examines the interactions between plasma high density lipoprotein (HDL) metabolism and whole-body cholesterol economy. More specifically, this review addresses three questions: 1) does plasma HDL-C concentration correlate with the parameters of whole-body cholesterol metabolism? 2) Do variations in cholesterol metabolism interfere with plasma HDL-C concentrations? 3) Are the markers of cholesterol synthesis and intestinal absorption specifically under the control of plasma HDL? The following answers were provided to each question, respectively: 1) plasma HDL influences whole-body cholesterol synthesis rate but the evidence that HDL modifies the total amount of cholesterol absorbed by the intestine is not clearly supported by present investigations; 2) there are suggestions that changes in whole body cholesterol metabolism rates do not interfere with plasma HDL-C concentrations; 3) markers of cholesterol synthesis and absorption may specifically be controlled by plasma HDL-C concentrations regarding the genetic causes of extremely low HDL-C concentrations, although within the general population plasma HDL-C concentration is likely ascribed to insulin resistance or diabetes mellitus.


Molecular pathology and pathobiology of osteoarthritic cartilage.
The biochemical properties of articular cartilage rely on the biochemical composition and integrity of its extracellular matrix. This matrix consists mainly of a collagen network and the proteoglycan-rich ground substance. In osteoarthritis, ongoing cartilage matrix destruction takes place, leading to a progressive loss in joint function. Beside the degradation of molecular matrix components, destabilization of supramolecular structures such as the collagen network and changes in the expression profile of matrix molecules also take place. These processes, as well as the pattern of cellular reaction, explain the pathology of osteoarthritic cartilage degeneration. The loss of histochemical proteoglycan staining reflects the damage at the molecular level, whereas the supramolecular matrix destruction leads to fissuring and finally to the loss of the cartilage. Chondrocytes react by increasing matrix synthesis, proliferating, and changing their cellular phenotype. Gene expression mapping in situ and gene expression profiling allows characterization of the osteoarthritic cellular phenotype, a key determinant for understanding and manipulating the osteoarthritic disease process.