Prognostic value of different N1 lymph node zones in pN1M0 non-small cell lung cancer: a systematic review and meta-analysis.
The IASLC lymph node map grouped the lymph node stations into "zones" for prognostic analyses. In the N1 lymph nodes group, N1 nodes are divided into the Hilar/Interlobar zone (N1h) and Peripheral zone (N1p). There is no consensus on the different prognostic values of N1 lymph nodes in N1h and N1p. Therefore, we conducted a systematic review and meta-analysis to assess the survival difference between N1h and N1p in patients of pN1M0 NSCLC. Medline, the Cochrane Library, Embase, and the Web of science were systematically searched to identify relevant studies published up to April 4th, 2020. A retrospective and prospective cohort study comparing N1h versus N1p to the pN1M0 NSCLC was included. Hazard ratios (HRs) for OS were aggregated according to a fixed or random-effect model. Ten publications for 1946 patients of pN1M0 NSCLC were included for the meta-analysis.The 5-year OS was lower for patients with N1h (HR: 1.67, 95% CI 1.44-1.94; P < 0.001). The pooled 5-year OS in N1h and N1p were 40% and 56%, respectively. The patients in pN1M0 NSCLC have different survival according to different N1 lymph node zones involvement: patients with N1p metastasis have a better prognosis than those with N1h metastasis.


Glutathione-S-transferase M1 polymorphism and pro-inflammatory cytokines tumour necrosis factor-α and interleukin-1β are associated with preeclampsia in Serbian women.
Preeclampsia has a multifactorial origin with genetic, immunological, and environmental factors described as main contributors to its onset. This study aimed to investigate glutathione-S-transferase M1 (GSTM1) and glutathione-S-transferase T1 (GSTT1) gene polymorphisms, the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and the potential relationship between GST polymorphisms and cytokine expression levels in preeclampsia and uncomplicated pregnancy. This prospective case-control study included 50 women with preeclampsia and 50 healthy pregnant women. DNA and RNA were extracted from women leukocytes. Deletion polymorphisms were analyzed by PCR, while cytokine mRNA expression was analyzed by real-time PCR. GSTM1 null genotype with present GSTT1 increased the risk for preeclampsia development. Deletion of GSTT1 without deletion of GSTM1 increased the risk for early preeclampsia. Relative mRNA expression of TNF-α was significantly higher in preeclampsia compared to healthy pregnant women (P = 0.006). Expression of IL-1β was significantly higher in severe and late preeclampsia compared to the control group (P = 0.005, P = 0.007, respectively). A significant positive correlation between TNF-α and IL-1β was observed (Spearman's ρ = 0.312, P = 0.028) and between IL-1β and IL-6, in preeclampsia group (Spearman's ρ = 0.296, P = 0.037). IL-1β was significantly increased in patients with GSTT1 null genotype (P = 0.015) while IL-6 was increased in patients with GSTM1 null genotype (P = 0.015). GSTM1 null genotype represents a risk factor for preeclampsia development, while GSTT1 null genotype favors early preeclampsia. Preeclampsia is also associated with increased expression of pro-inflammatory cytokines, predominantly TNF-α and IL-1β.


Trends in cancer incidence in metropolitan Detroit, 1937--1977: leads for prevention.
Cancer incidence among the black and white male and female population of metropolitan Detroit is presented for the years 1937, 1948, 1969--1971, and 1973--1977. These trends reveal increases in lung cancer among all four groups over time, while stomach cancers have decreased among each of the four groups. For black and white men lung cancer has the highest incidence in the two recent time periods, while cancer of the prostate was highest in the two earlier time periods. Among women, uterine cancer had the highest incidence for both blacks and whites in the earlier time periods, but breast cancer occurred among women more frequently than any other cancer in the most recent time period. These trends reveal the changing incidence patterns over time within an urban, industrialized population. Population-based cancer incidence data provide the most complete and accurate assessment of the occurrence of cancer within a population. Such data are particularly useful for proper planning of screening programs and for evaluating the need for preventive measures. As an example, the continuous increase in lung cancer in all four groups across all time periods clearly reveals the need for more effective measures to reduce cigarette smoking in this population.


Complex changes in alternative pre-mRNA splicing play a central role in the epithelial-to-mesenchymal transition (EMT).
The epithelial-to-mesenchymal transition (EMT) is an important developmental process that is also implicated in disease pathophysiology, such as cancer progression and metastasis. A wealth of literature in recent years has identified important transcriptional regulators and large-scale changes in gene expression programs that drive the phenotypic changes that occur during the EMT. However, in the past couple of years it has become apparent that extensive changes in alternative splicing also play a profound role in shaping the changes in cell behavior that characterize the EMT. While long known splicing switches in FGFR2 and p120-catenin provided hints of a larger program of EMT-associated alternative splicing, the recent identification of the epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) began to reveal this genome-wide post-transcriptional network. Several studies have now demonstrated the truly vast extent of this alternative splicing program. The global switches in splicing associated with the EMT add an important additional layer of post-transcriptional control that works in harmony with transcriptional and epigenetic regulation to effect complex changes in cell shape, polarity, and behavior that mediate transitions between epithelial and mesenchymal cell states. Future challenges include the need to investigate the functional consequences of these splicing switches at both the individual gene as well as systems level.


Aggregation as bacterial inclusion bodies does not imply inactivation of enzymes and fluorescent proteins.
Many enzymes of industrial interest are not in the market since they are bio-produced as bacterial inclusion bodies, believed to be biologically inert aggregates of insoluble protein. By using two structurally and functionally different model enzymes and two fluorescent proteins we show that physiological aggregation in bacteria might only result in a moderate loss of biological activity and that inclusion bodies can be used in reaction mixtures for efficient catalysis. This observation offers promising possibilities for the exploration of inclusion bodies as catalysts for industrial purposes, without any previous protein-refolding step.


[Medical corrective make-up in post- chemotherapy].
Medical corrective make up can be applied to hide the adverse effects of cancer treatments. The aim of this study was to evaluate the tolerance and the satisfaction of patients needing medical make up to hide the cutaneous side effects induced by chimiotherapy and to improve self-esteem. 90 cancer patients were included in this multicentric study. They were being treated by chimiotherapy and had eyebrow alopecia, complexion changes, irregular lip contour or lip dryness. They were made up by socio-esthecians. Photos were taken before and after applications of make up. The patients had to fill in a self-questionnaire at home. The duration of the study varied from 1 to 4 weeks. Included patients were 52 years old. Tolerance was considered to be satisfactory or very satisfactory by 95,4% and 98,9% of the patients for eyebrow pencil corrector and the dual lip and contour corrector, respectively. Questions on quality of live and self-esteem revealed that the medical corrective make up improved the quality of life in general for 81,2% of the patients. This product range enhanced the self-esteem of 76,8% of the patients. Cosmetic agreement was highly satisfactory. In this study in which patients were suffering from cancer and treated by chimiotherapy, we showed that medical corrective make up can improve the quality of life with a very good tolerance.


Comparison of roadside crash injury metrics using event data recorders.
The occupant impact velocity (OIV) and acceleration severity index (ASI) are competing measures of crash severity used to assess occupant injury risk in full-scale crash tests involving roadside safety hardware, e.g. guardrail. Delta-V, or the maximum change in vehicle velocity, is the traditional metric of crash severity for real world crashes. This study compares the ability of the OIV, ASI, and delta-V to discriminate between serious and non-serious occupant injury in real world frontal collisions. Vehicle kinematics data from event data recorders (EDRs) were matched with detailed occupant injury information for 180 real world crashes. Cumulative probability of injury risk curves were generated using binary logistic regression for belted and unbelted data subsets. By comparing the available fit statistics and performing a separate ROC curve analysis, the more computationally intensive OIV and ASI were found to offer no significant predictive advantage over the simpler delta-V.


A simple method to assess in vivo repair of ultraviolet radiation-induced lesions of specific DNA sequences of restriction sites.
Based on the direct relationship between ultraviolet irradiation of DNA and its susceptibility to restriction endonucleases, we have devised a simple method to quantify in vivo damage and repair of selected restriction sites. The simplicity and power of the method were demonstrated with HindIII restriction endonuclease and pAc360-501-beta-gal plasmid in UV-irradiated Escherichia coli cells. The large number of available restriction endonucleases makes the method quite flexible. This method provides a simple and inexpensive means to screen mutagenic and antimutagenic drugs that interact with the DNA repair mechanism.


Hypothalamic abnormalities in patients with pituitary-dependent Cushing's syndrome.
We aimed to investigate the pattern of 24-hour ACTH and cortisol secretion in pituitary-dependent Cushing's syndrome and to evaluate the pituitary and hypothalamic contributions to the disease. Five women with Cushing's disease (mean age 35 +/- 5 (SEM) years) and five normal female controls (mean age 25 +/- 2 years) were studied. Plasma ACTH and cortisol levels were measured every 15 minutes for 24 hours using established IRMA and RIA respectively. ACTH and cortisol mean and trough levels, pulse number and amplitude were calculated using established computer software, programmed to identify ACTH and cortisol peaks. Patients with Cushing's disease had a twofold increase in 24-hour mean cortisol levels and a threefold increase in 24-hour mean ACTH levels (Cushing's 5.9 +/- 1.0, controls 1.9 +/- 0.2 pmol/l, P less than 0.01). This was predominantly mediated by an increase in ACTH pulse amplitude. However, 24-hour ACTH pulse number was also increased (Cushing's 15.2 +/- 2.6, controls 10.6 +/- 1.7, P less than 0.05) due to an increase in pulse number between 1800 and 2400 h. ACTH trough levels were also higher in patients with Cushing's disease (Cushing's 5.3 +/- 1.3, controls 2.3 +/- 0.2 pmol/l, P less than 0.05). Twenty-four-hour mean plasma cortisol and ACTH levels are elevated two to three-fold in patients with Cushing's disease. The increase in ACTH pulse amplitude suggests a pituitary abnormality in patients with Cushing's disease. However, the increased ACTH pulse frequency together with elevated trough levels is interpreted as indicating coexisting hypothalamic stimulation (or loss of inhibition).


Functional recovery after destruction of dopamine systems in the nucleus accumbens of rats. I. Behavioral and biochemical studies.
Bilateral 6-hydroxydopamine (6-OHDA) lesions in the nucleus accumbens of rats induced motor hypoactivity 7 days after the lesion. Spontaneous functional recovery of this impaired behavior occurred in 3-4 weeks. Behavioral and biochemical studies suggest that the hypoactivity is due to damage of the dopamine systems in the nucleus accumbens. The 6-OHDA lesions induced a decrease in the nucleus accumbens levels of dopamine and its metabolites of about 30% both 7 and 20 days after the lesion. The in vitro uptake of [3H]dopamine in nucleus accumbens tissue of the 6-OHDA-lesioned rats was decreased to the same extent at 7, 14 and 28 days after the lesion. Scatchard analysis of [3H]haloperidol binding studies in nucleus accumbens tissue revealed a shift from one type of binding site in tissue of sham-lesioned rats to two types of binding sites in tissue of 6-OHDA-lesioned rats 29 days after the lesion. This shift was not present in nucleus accumbens tissue 8 days after a 6-OHDA lesion. The spontaneously recovered rats showed an enhanced behavioral response upon administration of the dopamine agonist apomorphine. The present data suggest that the spontaneous functional recovery of impaired motor activity is caused by the development of supersensitivity of the dopamine receptor systems in the nucleus accumbens. This supersensitivity may be the result of increased affinity of one type of binding site or an increased number of functional binding sites.


Epidemiology of diabetic kidney disease in adult patients with type 1 diabetes in Italy: The AMD-Annals initiative.
Patients with type 1 diabetes mellitus are at increased risk of death. This risk appears to be modulated by kidney dysfunction. The aim of this study was to evaluate the prevalence of diabetic kidney disease (DKD), its traits, and clinical correlates in a large sample of patients with type 1 diabetes. Clinical data of 20 464 patients with type 1 diabetes were extracted from electronic medical records. Estimated glomerular filtration rate (eGFR) and increased urinary albumin excretion were considered. Mean age of the patients was 46 ± 16 years, 55.0% were males, and duration of diabetes 19 ± 13 years. The frequency of diabetic kidney disease, low eGFR, and albuminuria was 23.5%, 8.1%, and 19.5%, respectively. In the multivariate analysis the presence of diabetic kidney disease was associated with age (odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.10-1.18), duration of diabetes (OR = 1.05, 95% CI: 1.03-1.07), and worse glycemic control (OR = 1.24, 95% CI: 1.21-1.28, for every 1% glycated hemoglobin increase). Diabetic kidney disease was also independently associated with an atherogenic lipid profile and increased systolic blood pressure. Glucose control, systolic blood pressure, triglycerides, and high density lipoprotein cholesterol were associated with both low eGFR and albuminuria. Male gender, retinopathy and smoke were related to albuminuria, being female was related to low eGFR, while SUA levels were associated with DKD, low eGFR and albuminuria. In our sample of patients with type 1 diabetes, diabetic kidney disease entails an unsafe cardiovascular risk profile. Hyperglycemia, arterial hypertension, and atherogenic lipid profile affected both low eGFR and albuminuria. Retinopathy and smoking were related only to albuminuria while being female and elevated serum uric acid were associated only with low eGFR.


Thrombectomy in posterior circulation stroke: differences in procedures and outcome compared to anterior circulation stroke in the prospective multicentre REVASK registry.
In contrast to anterior circulation stroke (ACS), there is no evidence from randomized trials that mechanical thrombectomy (MT) with modern stent retrievers or thromboaspiration is safe and effective in posterior circulation stroke (PCS). The present analysis was based on the prospective multicentre Registry on Revascularization in Ischemic Stroke Patients (REVASK) in Germany. Demographic data, periprocedural times and complications, recanalization rates, and functional outcome at discharge and after 3 months were compared between 139 consecutive patients with PCS (84.9% basilar artery, 16.5% vertebral artery and 4.3% posterior cerebral artery occlusion) and 961 patients with ACS treated with MT. Compared to ACS, PCS patients were significantly younger (65 vs. 69 years, P = 0.021) and had a lower median National Institutes of Health Stroke Scale (NIHSS) score at baseline (12 vs. 15, P = 0.024). Patients with PCS had a significantly longer time delay between symptom onset and both start and end of the MT procedure. Successful recanalization and thrombectomy passes did not significantly differ between the two groups. No symptomatic intracranial haemorrhage occurred in PCS compared to 3% in ACS (P = 0.010). The median NIHSS score at discharge was 3 in PCS and 4 in ACS. Favourable functional outcome at 3 months (modified Rankin Scale 0-2 38.0% vs. 42.6%, P = 0.392) and mortality (33.7% vs. 30.8%, P = 0.539) did not differ significantly between PCS and ACS. The study suggests that MT in PCS shows a lower risk of symptomatic intracranial haemorrhage and similar effectiveness compared to ACS. PCS patients also seem to benefit from MT started beyond 6 h after symptom onset.


Recovery of phosphorus rich krill shell biowaste for uranium immobilization: A study of sorption behavior, surface reaction, and phase transformation.
Increased generation of shrimp shell from exploitation of krill results in emerging biowaste pollution, in addition, uranium pollution has drawn public concern due to the rapid development of nuclear power, uranium mining, and nuclear fuel processing. In this study, krill shells were recovered and used as a potential natural biosorbent for uranium immobilization, thereby enabling both uranium decontamination and krill shell reutilization. Interaction of uranium with krill shell surface and their transformation were investigated by using batch sorption experiments, scanning electron microscopy, and transmission electron microscopy. Krill shell had high uranium sorption ability. Uranium was transformed into a nano-scale precipitate. The mapping of phosphorus and uranium was related to the nano-scale precipitate, indicating that sorption of uranium was dependent on phosphorus. Surface chemisorption between phosphate in krill shell and uranium as well as the formation of the nano-scale precipitate were interpreted as the mechanism of uranium immobilization. Thus, natural krill shell waste has potential for extensive use as a promising and cost-effective sorbent for uranium immobilization and krill shell reutilization.


Lactic acid permeation rate in working gastrocnemii of dogs during metabolic alkalosis and acidosis.
In isolated, blood perfused, supramaximally stimulated, isotonically working gastrocnemii of dogs lactic acid (LA) output and O2-consumption (V O2) were measured according to the Fick principle. Simultaneously concentration of muscle tissue was determined at rest and at different times during exercise. In one series of experiments metabolic alkalosis was induced by infusions of THAM of Na bicarbonate. As a result arterial pH increased to about 7.5 and standard [HCO3-1] to 31-35 mmol per 1. In another group of experiments metabolic acidosis was induced by HCl infusions. In these experiments pH decreased to 7.0-7.1 and standard [HO301] to 8-11 mmol per 1. During the first 3-4 min after the onset of exercise LA concentration of muscle tissue rose to 18-19 mumol per g wet weight in both series of experiments. During acidosis the highest average values for LA release from the muscle were about 1.1 mumoles per g per minute. During alkalosis LA permeation rate was nearly three times as high. As a consequence of increased rate of permeation, LA concentration of muscle tissue decreased more rapidly in alkalosis than in acidosis. In both series of experiments work per time and VO2 were practically equal during the first 5-6 min of exercise. Thereafter work per time and VO2 decreased more rapidly in acidosis than in alkalosis, a result which probably is due to higher LA concentration in muscle at this time in acidosis. It is concluded that LA permeation rate across muscle cell membrane is increased by high extracellular HCO3- concentration in combination with low H+ activity and vice versa.


A new natural reservoir of hantavirus: isolation of hantaviruses from lung tissues of bats.
Two species of bats were confirmed as new natural reservoirs of hantavirus. Antibodies to Hantaan virus were detected in 3.40% (23 of 677) of bats captured from 1989 to 1992 in Korea by the IFA technique. Areal distribution of immunofluorescent antibody were different, and seropositive rates were much high in sera of bats captured in summer (3.82%) and winter (5.82%). Viral antigens were observed in the lungs (3 of 16) and kidney (1 of 7). Two hantaviruses were isolated from lung tissues of E. serotinus and R. ferrum-equinum through a cell culture system, designated CUMC-92B8 and -92B48, respectively. Using Rous associated virus-2 reverse transcriptase-directed PCR and 2 oligonucleotide primer pairs, genomic sequences of the isolates were amplified. Amplified products of the isolates and reactivities to monoclonal antibodies very closely resembled those of Hantaan virus. These data suggest that the serotype of the isolates is closely related to Hantaan virus, and bats serve as reservoirs of hantavirus.


Calcium-independent phospholipases A2 in murine osteoblastic cells and their inhibition by bromoenol lactone: impact on arachidonate dynamics and prostaglandin synthesis.
Bromoenol lactone (BEL) is an inhibitor of group VI phospholipases (iPLA2s), but has been shown to have severe side effects. iPLA2 characterization in osteoblasts and effect of BEL on prostaglandin (PG) E2 formation. iPLA2 expression: RT-PCR, Western Blotting. PGE2 formation: GC-MS after stimulation, treatment with inhibitors or gene silencing. Arachidonate (AA) reacylation into phospholipids, inhibitor reaction products, PGHS-1 modification proteomic analysis: HR-LC-MS/MS. AA accumulation: (14)C-AA. iPLA2ß and iPLA2γ were expressed and functionally active. BEL inhibition up to 20 μM caused AA accumulation and enhanced PGE2 formation, followed by a decrease at higher concentrations. BEL reacted with intracellular cysteine and GSH leading to GSH depletion and oxidative stress. Initial PGE2 enhancement after BEL inhibition is due to iPLA2-independent accumulation of AA. GSH depletion caused by high BEL concentrations is responsible for the decrease in PGE2 production. BEL must be used with caution in a cellular environment due to conditions of extreme oxidative stress.


The diagnostic utility of diffusion-weighted magnetic resonance imaging and high-resolution computed tomography for cholesteatoma: A meta-analysis.
The purpose of this meta-analysis was to compare the efficiency of high-resolution computed tomography (HRCT) and diffusion-weighted magnetic resonance imaging (DWI) in guiding the diagnosis of middle ear cholesteatoma in clinical practice. Cochrane Library, Medline, Embase, PubMed, and Web of Science were searched for studies that evaluated the sensitivity and specificity of HRCT or DWI in detecting middle ear cholesteatoma. A random-effects model was used to calculate and summarize the pooled estimates of sensitivity, specificity, and diagnostic odds ratios. Postoperative pathological results were considered as the diagnostic gold standard for middle ear cholesteatoma. Fourteen published articles (860 patients) met the inclusion criteria. The sensitivity and specificity of DWI when diagnosing cholesteatoma (regardless of type) were 0.88 (95% confidence interval [CI], 0.80-0.93) and 0.93 (95% CI, 0.86-0.97), respectively, while those of HRCT were 0.68 (95% CI, 0.57-0.77) and 0.78 (95% CI, 0.60-0.90), respectively. Notably, the sensitivity and specificity levels of DWI were similar to those of HRCT (p = .1178 for sensitivity, p = .2144 for specificity; pair-sampled t tests). The sensitivity and specificity of DWI or HRCT for the diagnosis of primary cholesteatoma were 0.78 (95% CI, 0.65-0.88) and 0.84 (95% CI, 0.69-0.93), respectively, while that for recurrent cholesteatoma were 0.93 (95% CI, 0.61-0.99) and 0.94 (95% CI, 0.82-0.98), respectively. DWI and HRCT have similar levels of high sensitivity and specificity in detecting various cholesteatomas. Also, the diagnostic efficiency of HRCT or DWI for recurrent cholesteatoma is identical to that of primary cholesteatoma. Therefore, HRCT may be used in clinical settings to reduce the use of DWI and save clinical resources. Data on the use of diffusion-weighted magnetic resonance imaging and high-resolution computed tomography in the diagnosis of cholesteatoma were obtained through a literature search. They were analyzed to guide the clinical diagnosis and treatment of cholesteatoma. NA.


[Invasive cancer of the prostate. Reconstruction of the lower urinary tract by prostatic resection and ureteral reimplantation into the bladder vault].
Some prostatic cancers (T4) spread out along the ureters to the kidneys. Patients, usually arrive with terminal renal failure and bladder retention and have often fast-advancing cancer with massive nodes invading. T.U.R., reimplantation of the ureters into the bladder dome or into a psoïc bladder and the specific treatment of the cancer, have often permitted these patients to survive for some years without any dialysis. In these cases we often find very important lower limbs oedema. With lymphatic nodes radiotherapy and subcutaneous injections of heparin, these oedema may regress completely.


Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma.
It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States. We conducted a case-control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor. Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P < 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively. In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals. The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.


Genome sequence of Corynebacterium glutamicum ATCC 14067, which provides insight into amino acid biosynthesis in coryneform bacteria.
We report the genome sequence of Corynebacterium glutamicum ATCC 14067 (once named Brevibacterium flavum), which is useful for taxonomy research and further molecular breeding in amino acid production. Preliminary comparison with those of the reported coryneform strains revealed some notable differences that might be related to the difficulties in molecular manipulation.


A panel of diverse Klebsiella pneumoniae clinical isolates for research and development.
Klebsiella pneumoniae are a leading cause of healthcare-associated infections worldwide. In particular, strains expressing extended-spectrum β-lactamases (ESBLs) and carbapenemases pose serious treatment challenges, leading the World Health Organization (WHO) to designate ESBL and carbapenem-resistant Enterobacteriaceae as 'critical' threats to human health. Research efforts to combat these pathogens can be supported by accessibility to diverse and clinically relevant isolates for testing novel therapeutics. Here, we describe a panel of 100 diverse K. pneumoniae isolates that are publicly available to assist the research community in this endeavour. Whole-genome sequencing (WGS) was performed on 3878 K. pneumoniae clinical isolates housed at the Multidrug-Resistant Organism Repository and Surveillance Network. The isolates were cultured from 63 facilities in 19 countries between 2001 and 2020. Core-genome multilocus sequence typing and high-resolution single-nucleotide polymorphism-based phylogenetic analyses captured the genetic diversity of the collection and were used to select the final panel of 100 isolates. In addition to known multidrug-resistant (MDR) pandemic lineages, the final panel includes hypervirulent lineages and isolates with specific and diverse resistance genes and virulence biomarkers. A broad range of antibiotic susceptibilities, ranging from pan-sensitive to extensively drug-resistant isolates, are described. The panel collection, and all associated metadata and genome sequences, are available at no additional cost and will be an important resource for the research community and for the design and development of novel antimicrobial agents and diagnostics against this important pathogen.


Gastrointestinal helminths of little blue penguins, Eudyptula novaehollandiae (Stephens), from Otago, New Zealand.
Data regarding helminth communities can provide insights into health, feeding interactions, behaviour and evolution of their host organisms. Penguins (Spheniscidae) are important components of marine food webs and tracking their helminth communities can be indicative of ecosystem health. New Zealand is home to 5 of the world's 19 penguin species and little is known about their gastrointestinal helminths. Here, we provide the first study on the gastrointestinal helminths of little blue penguins from south-eastern South Island, New Zealand. The helminth community consisted of two species of tapeworm; Tetrabothrius lutzi and Tetrabothrius sp.; three nematode species, Contracaecum eudyptulae, Capillaria sp. and Stegophorus macronectes; two acanthocephalans, Andracantha sigma and Bolbosoma balaenae; and one trematode, Galactosomum otepotiense. The most prevalent parasites were T. lutzi, A. sigma, and C. eudyptulae. This work includes three new host records and five new geographic records. This is the first report of B. balaenae occurring in a host other than a marine mammal. This study adds to our knowledge about the helminth community of New Zealand little blue penguins, and includes new genetic data on helminth species, providing a baseline against which future studies may be compared.


Changing concepts in establishing the diagnosis of breast masses.
Experience with 297 consecutive biopsies of breast masses for 235 benign lesions and 62 carcinomas over a thirty month period has been reviewed. The correct preoperative clinical diagnosis was made in 91% of cases. Of patients with carcinoma, 66% were suspected clinically, and 88% of those clinically suspected were confirmed by needle biopsy alone. The mammographic diagnosis was correct in 89% of cases with 6% false-negatives. The clinical and mammographic diagnosis differed in 27 patients, with the clinical diagnosis being correct in 85%. No patient thought to have cancer on both clinical and mammographic grounds had a benign lesion. These data indicate that the approach to establishing a tissue diagnosis in women with breast masses can be simple and inexpensive. Local anesthesia can almost always be employed, and the diagnosis of breast cancer can usually be confirmed with certainty by needle biopsy alone.


Use of digital technology in prosthesis fabrication for an elderly patient with a maxillectomy and severe trismus: A clinical report.
This clinical report describes a novel approach based on digital technology to fabricate a maxillofacial prosthesis for a 90-year-old woman with severe trismus who had undergone maxillectomy on the right side. The approach was safe, rapid, and less burdensome on this elderly patient, and the storage and communication of intraoral and maxillofacial prosthesis data without temporal and spatial constraints was helpful. A combination of digital and analog technology provided a maxillofacial prosthesis that improved the quality of life of this elderly patient with head and neck cancer and severe trismus.


Degradation of bovine C3 by serine proteases from parasites Hypoderma lineatum (Diptera, Oestridae).
Purified enzymes of Hypoderma lineatum (Insecta, Oestridae), were assayed for their proteolytic activity on bovine C3 in normal cattle sera. The products of cleavage by these serine proteases (hypodermins A, B, and C), were analysed by electrophoresis in SDS polyacrylamide gels followed by immunoblotting. The enzymatic attack was initially directed at the alpha polypeptide chain by hypodermin A at a concentration of 1 micrograms/ml of serum and by hypodermin B at 5 micrograms/ml. The generated peptides differed in their molecular size from those produced during natural degradation of C3 in a control serum by physiologically relevant enzymes. Hypodermin A, at a concentration of 1 microgram/ml, also caused a cleavage of the beta chain. At 5 micrograms/ml, hypodermin A induced total degradation of the C3 molecule. Hypodermin B (5 micrograms/ml) starts splitting C3 near cleavage sites of factor I. Bovine C3 appears to be highly sensitive to hypodermins A and B in normal sera. Apparent molecular sizes and alignment of the bovine C3 cleavage products are presented schematically. Hypodermin C, a collagenolytic enzyme, had no effect on C3 in normal sera. The biological consequences for the immunopathological reactions associated with hypodermosis are discussed.


Ovarian hyperthecosis associated with fatty liver disease.
Both cirrhosis and chronic active hepatitis have been reported in patients having ovarian hyperthecosis. This case report now documents histologically verified coincidental fatty liver disease along with ovarian hyperthecosis in a patient having an 8-year evolution of abnormal liver tests, hirsutism, and irregular menses.


A multicenter, randomized, double-blind, retrospective comparison of 5- and 10-day regimens of levofloxacin in a subgroup of patients aged > or =65 years with community-acquired pneumonia.
This subgroup analysis sought to determine the efficacy and tolerability of a 5-day regimen of levofloxacin 750 mg/d compared with a 10-day regimen of levofloxacin 500 mg/d in the treatment of community-acquired pneumonia (CAP) in elderly patients (aged > or =65 years). This subgroup analysis was based on the outcomes in patients aged > or =65 years from a randomized, double-blind, controlled trial conducted at 70 US centers. Patients in Pneumonia Severity Index (PSI) class I/II and III/IV were randomized to receive levofloxacin 750 mg/d for 5 days or levofloxacin 500 mg/d for 10 days. Study investigators assessed clinical and microbiologic outcomes 7 to 14 days after administration of the last dose of medication and collected adverse events for 30 days after the last dose. This analysis included 177 elderly patients, 80 receiving levofloxacin 750 mg/d for 5 days and 97 receiving levofloxacin 500 mg/d for 10 days. Although most demographic and baseline clinical characteristics were comparable between the 2 groups, the group that received levofloxacin 500 mg/d was older than the group that received levofloxacin 750 mg/d (median age, 76.0 vs 72.5 years, respectively; P = 0.029) and had a higher mean PSI score (90.7 vs 83.1; P = 0.017). Despite the halved duration of therapy, unadjusted clinical success rates were comparable between the 2 groups (89.0% and 91.9% in the 750- and 500-mg arms, respectively; 95% CI, -7.1 to 12.7). Microbiologic eradication rates were 90.3% (28/31) in the 750-mg arm and 87.5% (14/16) in the 500-mg arm (P = NS). Multivariate analysis adjusting for baseline PSI score indicated that treatment assignment was not statistically associated with clinical success (adjusted odds ratio for clinical success with 500-mg dose, 1.92; 95% CI, 0.62 to 5.99). The incidence of treatment-emergent adverse events did not differ between the 2 study treatments. The most common adverse events in both groups were insomnia, constipation, and headache. This subgroup analysis found that levofloxacin 750 mg/d for 5 days was well tolerated in the treatment of CAP in elderly patients. Undajusted and adjusted rates of clinical success were statistically similar between levofloxacin 750 mg/d for 5 days and levofloxacin 500 mg/d for 10 days.


Biogenesis of cytochrome c oxidase.
Cytochrome c oxidase (COX), the terminal enzyme of electron transport chains in some prokaryotes and in mitochondria, has been characterized in detail over many years. Recently, a number of new data on structural and functional aspects as well as on COX biogenesis emerged. COX biogenesis includes a variety of steps starting from translation to the formation of the mature complex. Each step involves a set of specific factors that assist translation of subunits, their translocation across membranes, insertion of essential cofactors, assembly and final maturation of the enzyme. In this review, we focus on the organization and biogenesis of COX.


Multicenter clinical radiomics-integrated model based on [18F]FDG PET and multi-modal MRI predict ATRX mutation status in IDH-mutant lower-grade gliomas.
To develop a clinical radiomics-integrated model based on 18 F-fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and multi-modal MRI for predicting alpha thalassemia/mental retardation X-linked (ATRX) mutation status of IDH-mutant lower-grade gliomas (LGGs). One hundred and two patients (47 ATRX mutant-type, 55 ATRX wild-type) diagnosed with IDH-mutant LGGs (CNS WHO grades 1 and 2) were retrospectively enrolled. A total of 5540 radiomics features were extracted from structural MR (sMR) images (contrast-enhanced T1-weighted imaging, CE-T1WI; T2-weighted imaging, and T2WI), functional MR (fMR) images (apparent diffusion coefficient, ADC; cerebral blood volume, CBV), and metabolic PET images ([18F]FDG PET). The random forest algorithm was used to establish a clinical radiomics-integrated model, integrating the optimal multi-modal radiomics model with three clinical parameters. The predictive effectiveness of the models was evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA). The optimal multi-modal model incorporated sMR (CE-T1WI), fMR (ADC), and metabolic ([18F]FDG) images ([18F]FDG PET+ADC+ CE-T1WI) with the area under curves (AUCs) in the training and test groups of 0.971 and 0.962, respectively. The clinical radiomics-integrated model, incorporating [18F]FDG PET+ADC+CE-T1WI, three clinical parameters (KPS, SFSD, and ATGR), showed the best predictive effectiveness in the training and test groups (0.987 and 0.975, respectively). The clinical radiomics-integrated model with metabolic, structural, and functional information based on [18F]FDG PET and multi-modal MRI achieved promising performance for predicting the ATRX mutation status of IDH-mutant LGGs. • The clinical radiomics-integrated model based on [18F]FDG PET and multi-modal MRI achieved promising performance for predicting ATRX mutation status in LGGs. • The study investigated the value of multicenter clinical radiomics-integrated model based on [18F]FDG PET and multi-modal MRI in LGGs regarding ATRX mutation status prediction. • The integrated model provided structural, functional, and metabolic information simultaneously and demonstrated with satisfactory calibration and discrimination in the training and test groups (0.987 and 0.975, respectively).


Reference value of presenile human hematocrit and geographical factors.
The aim of this study was to provide a scientific basis for a unified standard of the reference value of healthy presenile human hematocrit in China. We studied the relationship between the reference values of healthy presenile human hematocrit, tested according to Wintrobe's laws, and five geographical factors. It was found that altitude is the most important factor affecting the reference value of the hematocrit. As the altitude gradually increases, the reference value of the hematocrit also increases. The relationship is quite significant. By using the method of stepwise regression analysis, two multivariate regression equations were deduced: Y1 = 39.7 + 0.00328X1 + 0.00169X2 + 0.00117X5 +/- 2.3, Y2 = 38.8 + 0.00275X1 + 0.000578X2 -0.00298X4 +/- 2.2 In these equations, Y1 is the reference value of presenile men's hematocrit (%); Y2 is the reference value of presenile women's hematocrit (%); X1 is altitude (m); X2 is the average annual hours of sunshine (h); X4 is the average annual temperature (degrees C), and X5 is the average annual precipitation (mm). If the geographical index values in a particular area in China are known, the reference value of presenile human hematocrit in this area can be calculated approximately by means of the regression equations.


Adrenalectomy, corticosteroid replacement and their importance for drug-induced memory-enhancement in mice.
Adrenalectomy blocks the memory-improving effect of piracetam-like compounds in mice. If this blockade is due to the removal of endogenous corticosteroids, replacement therapy with exogenous corticosteroids should reinstate the effects on memory. The present experiments were designed to determine the appropriate replacement dose (concentration in the drinking fluid) for corticosterone and aldosterone, the main corticosteroids in mice. Based on the effects of corticosterone on thymus weight, replacement with 3 micrograms/ml corticosterone given in the drinking fluid (0.9% NaCl) for one week was found to be appropriate. The appropriate replacement dose for aldosterone was found by giving aldosterone to adrenalectomized (ADX) mice in the drinking fluid in combination with 3 micrograms/ml corticosterone. The combination of 3 micrograms/ml corticosterone + 30 ng/ml aldosterone resulted in a plasma ratio of corticosterone/aldosterone which most closely approximated the ratio seen in sham-ADX control animals. The physiologic adequacy of the corticosteroid replacement doses resulting from this study were clearly demonstrated in subsequent behavioral experiments where blockade of the memory-enhancing effects of piracetam by adrenalectomy were overcome by replacement with either 3 micrograms/ml corticosterone or 30 ng/ml aldosterone given in the drinking fluid.


Induction of proteinases in Legionella by growth on agar containing serum.
Non-proliferating cells of Legionella show a rather small proteolytic action on human serum proteins. However, if the strains grow on agar plates containing serum the proteolysis is very strong. This effect may be due to an induction of the appropriate enzymes by their substrates. The alterations of 24 investigated proteins demonstrated by immunoelectrophoresis show anodic shifts of bands and their disappearance (Table 1, Fig. 1-15). The shifted proteins are not degraded significantly. Their altered electrophoretic mobility may be due to a change of electrical charge by loss of one or a few end standing amino acids. The disappearance of bands in the immunoelectrophoretic assay and the simultaneous diminution of the protein concentration measured by the method of immunodiffusion suggests a proteolysis (Table 2). No inhibitory effect of the proteinase inhibitor aprotinin could be observed. The results suggest that the extent of the enzyme induction may be decisive for the virulence of a strain.


Non-invasive methods to measure inter-renal function in aquatic salamanders-correlating fecal corticosterone to the environmental and physiologic conditions of captive Necturus.
This study sought to develop non-invasive techniques to monitor glucocorticoids in captive Necturus as a means to correlate inter-renal gland function in relation to environmental and physiological changes. Six individually housed breeding pairs of captive Necturus beyeri were subjected to seasonal changes in water temperature (30°F temperature differential) to stimulate natural breeding, specifically spermatophore deposition and oviposition. An enzyme immunoassay was validated for the measurement of N. beyeri faecal corticosterone metabolites (fCMs) by exhibiting parallelism and accuracy to the standard curve. Longitudinal (December 2016-October 2017) assessment of fCM concentrations and pattern of excretion from samples collected from the six breeding pairs revealed a seasonal inter-renal effect with higher concentrations (P < 0.05) excreted during months (December-March) of the year associated with breeding activity and when water temperatures were lowest. Males from each pair produced spermatophores starting on 08 December 8 2016 and ending on 05 April 2017. Females from four of the six pairs went on to successfully oviposit eggs in mid-late April 2017. One clutch was fertile, and three were non-fertile. No differences (P > 0.05) were detected in fCM concentrations between pairs in which oviposition did or did not occur. In addition, a novel waterborne corticosterone metabolite (wCM) assay was validated to overcome challenges associated with faecal collection in a group-housed amphibian. An adrenocorticotropic hormone (ACTH) challenge performed in an adult male Necturus maculosus resulted in a 50-fold increase in wCM at 4 h post-injection and marked the first demonstration of a waterborne inter-renal response to ACTH in Necturus. This study not only provides insight into inter-renal function in an aquatic salamander that exhibits marked reproductive seasonality but also confirms utility of fCM and wCM measurements as non-invasive means of assessment.


Melatonin Does Not Affect Progesterone Basal Secretion but Suppresses the Luteinizing Hormone Receptor Expression in Granulosa Cells of the Japanese Quail.
The aim of this study was to evaluate the potential effect of melatonin on progesterone production by granulosa cells of the Japanese quail. For in vitro experiments, granulosa cells were isolated from pre-ovulatory follicles (F1-F3) when the F1 follicles were predicted to be either immature or mature (at 3-6 or 18-21 h after oviposition, respectively). Granulosa cells were cultured for 12 hwithor without melatonin concentration gradients of 0.0001-100 µg/mL, thereby averting luteinizing hormone (LH) stimulation. The concentration of progesterone in culture medium was measured using an enzyme immunoassay. The expression of melatonin receptor subtypes in granulosa cells from F1 follicles was detected by reverse transcription-PCR. The LH receptor (LHCGR) mRNA level in cultured granulosa cells of the F1 follicles was analyzed using quantitative real-time PCR. Six quails were used in each of four groups for in vivo experiments. Eachgroup received intraperitoneal injection of melatonin (0.67 mg/kg body weight) or mock-vehicle at 3 or 18 h after oviposition, respectively. The birds were decapitated to collect serum 3 hlater (at 6 or 21 h after oviposition, respectively). The serum progesterone level was also measured using an enzyme immunoassay. We observed that melatonin receptor subtypes (Mel-1a, 1b, and 1c) were expressed in the granulosa cells of the F1 follicles of the Japanese quail. Melatonin suppresses the LHCGR mRNA expression in granulosa cells of F1 follicles but does not affect the basal secretion of progesterone in cultured granulosa cells of the F1-F3 follicles. In addition, melatonin treatment has no influence on the serum progesterone concentration at 6 h post-oviposition, but suppresses progesterone level 21 h after oviposition in the Japanese quail.


[Epidemiological profile of Tinea capitis in Dakar (Senegal). A 6-year retrospective study (2008-2013)].
Tinea capitis is considered as a public health problem in Senegal. The aim of this study was to investigate trends in the incidence, the mycological and epidemiological aspects of tinea capitis diagnosed at Le Dantec Hospital in Dakar. Our work is a retrospective study concerning all scalp samples taken by the parasitology laboratory, over a 6-year period (2008-2013). A total of 1640 specimens were examined. Of these, 566 were positive with direct examination and after culture. We noted the reduction of patients and of the incidence of tineas during 6 years with variations of 147 (46.82%) to 37 (22.02%). The average incidence of the tineas during six years was 34.51%. Patients' age varied between 1 to 83 years with a mean of 27.33 years. Prevalence varied between age groups, with 10.61 % in adults between 20 to 29 years, 7.19% in children between 0 to 9 years, 6.04% between 10 to 19 years, and 5.91% in adults between 30 to 39 years. Women were more infected 469 (82.9%) than men 97 (17.1%). The main dermatophytes isolated were: T. soudanense in 318 cases (56.18%), T. rubrum in 104 cases (18.37%), M. langeronii in 72 cases (12.72%), M. canis in 36 cases (6.36%), and T. mentagrophytes in 26 cases (4.60%). Our study showed a decrease in the annual incidence of tinea capitis over the study period with an evident increase in trichophytic tinea. This study showed that tinea is endemic in Senegal mainly among women between 20 and 29 years.


Polychlorinated biphenyl (PCB) degradation and persistence of a gfp-marked Ralstonia eutropha H850 in PCB-contaminated soil.
Ralstonia eutropha H850 was labelled chromosomally with a gfp marker gene encoding for the green fluorescent protein, and designated R. eutropha H850g13. Visual observation of green fluorescent cells under an epifluorescence microscope, and PCR amplification products, confirmed that the bacterium was labelled with gfp. Southern blot hybridization products further confirmed the gfp was chromosomally labelled. Using resting cell assays, it was determined that insertion of the gfp gene decreased the microorganisms' ability to degrade biphenyl compared to the parent strain. However, this marker facilitated the identification and monitoring of R. eutropha H850g13 survival in soil microcosm experiments. Survival and polychlorinated biphenyl degradation by R. eutropha H850g13 was analysed in soil microcosms spiked with 2,2',5,5'-tetrachlorobiphenyl (TeCB). R. eutropha H850g13 was detected by viable plate counts and most-probable-number/PCR after 102 days in TeCB-contaminated soil microcosms, and was likely outcompeted by indigenous soil microorganisms in microcosms amended with oil and Daramend (an organic amendment, http://www.adventusremediation.com). R. eutropha H850g13 did not degrade TeCB in any of the soil microcosms. This research confirmed that gfp was useful as a marker to distinguish R. eutropha H850g13 from indigenous soil microorganisms over a 102 day period and that, under the experimental conditions used, R. eutropha H850g13 did not degrade TeCB.


Care for the "racially careless": Indian hospitals in the Canadian West, 1920-1950s.
In the 1930s, sanatorium directors and medical bureaucrats warned of the threat to Canadian society of "Indian tuberculosis." Long-standing government policy aimed to isolate Aboriginal people on reserves and in residential schools, while their access to medical care was limited by government parsimony and community prejudice. Characterized as "racially careless" concerning their own health, Aboriginal bodies were seen as a menace to their neighbours and a danger to the nation. By the 1940s state-run racially segregated Indian hospitals institutionalized Aboriginal people who were not welcome in provincial sanatoria or in the modernizing community hospitals. The opening of the Charles Camsell Indian Hospital in Edmonton in 1946, one of the first acts of the newly created department of National Health and Welfare, was a very public demonstration of the state's commitment to define and promote "national health" by isolating and institutionalizing Aboriginal people.


The controversial place of vitamin C in cancer treatment.
In 2008, we celebrate the 80th anniversary of the discovery of vitamin C. Since then, we know that vitamin C possesses few pharmacological actions although it is still perceived by the public as a "miracle-pill" capable to heal a variety of illnesses. Cancer is one of the most common diseases for which a beneficial role of vitamin C has been claimed. Thus, its dietary use has been proposed in cancer prevention for several years. Apart from this nutritional aspect, an extensive and often confusing literature exists about the use of vitamin C in cancer that has considerably discredited its use. Nevertheless, recent pharmacokinetic data suggest that pharmacologic concentrations of vitamin C can be achieved by intravenous injections. Since these concentrations exhibit anticancer activities in vitro, this raises the controversial question of the re-evaluation of vitamin C in cancer treatment. Therefore, the purpose of this commentary is to make a critical review of our current knowledge of vitamin C, focusing on the rationale that could support its use in cancer therapy.


Biochemical Profile by GC-MS of Fungal Biomass Produced from the Ascospores of Tirmania nivea as a Natural Renewable Resource.
The edible fruiting bodies of desert truffles are seasonally collected and consumed in many regions of the world. Although they are very expensive, they are bought and sold as a result of considerable scientific reports confirming their health and nutritional benefits. This study aimed to conduct laboratory production of the fungal biomass of Tirmania nivea as a natural renewable resource of many active biological compounds using an artificial growth medium. The T. nivea collected from Hafar Al-Batin, which is north of Saudi Arabia, and their ascospores were harvested and used to produce fungal biomass in potato dextrose broth. The cultivation was conducted using a shaking incubator at 25 °C for two weeks at 200 rpm. The crud extracts of the fungal biomass and mycelium-free broth were prepared using ethyl acetate, methanol and hexane. Preliminary gas chromatography-mass spectrometry (GC-MS) analysis and their biological activity as antimicrobial agents were investigated. The results showed that the crude extracts have biological activity against mold, yeast and bacteria. The preliminary GC-MS analysis reported that the fungal biomass and extracellular metabolites in the growth medium are industrial renewable resources of several biological compounds that could be used as antifungal, antibacterial, antiviral, anticancer, antioxidant, anti-trypanosomal and anti-inflammatory agents.


The combination of prazosin and verapamil in the treatment of essential hypertension.
An exaggerated fall in blood pressure has been reported with the combination of an alpha 1-blocker and a calcium antagonist. This study investigated, in a placebo-controlled, randomized crossover trial, the clinical usefulness of the combination of prazosin (2 mg b.i.d.) and verapamil (160 mg b.i.d.). Therapeutic efficacy was monitored at regular outpatient visits: average supine and erect blood pressures were, respectively, 175/99 and 176/103 mm Hg with placebo, 160/91 and 164/96 mm Hg with single drug treatment, and 152/84 and 152/89 mm Hg with combination therapy. This significant and clinically useful reduction in blood pressure had an overall magnitude of approximately 28/18 mm Hg (supine) and 29/19 mm Hg (erect). Further measurements were made during a series of intensive study days, and the most important additional finding was a pharmacokinetic interaction that resulted in increased peak concentrations and bioavailability of prazosin. In conclusion, the combination of prazosin and verapamil proved effective in the treatment of 12 patients with essential hypertension who had been poorly responsive to conventional treatment with a beta-blocker and thiazide diuretic.


Bisphosphonate treatment in chronic recurrent multifocal osteomyelitis.
To test the safety and efficacy of biphosphonates in chronic recurrent multifocal osteomyelitis (CRMO). Five patients with CRMO, all of whom had ongoing pain and loss of function despite conventional treatment with non-steroidal anti-inflammatory agents, were treated with pamidronate (1 mg/kg/dose with a dosing frequency of 2 to 4 monthly for a total treatment duration of 12 to 42 months). Pain decreased after the first infusion for 4 of 5 patients, with symptomatic improvement maintained with time. Significant improvement was seen in radiological lesions for these 4 patients. Bisphosphonates appear to be a useful and safe adjunctive treatment in CRMO when simple therapies such as anti-inflammatory agents fail to control symptoms or cases in which lesion expansion continues.


A systematic review and meta-analysis of changes in interleukin-8 levels in malaria infection.
The roles of interleukin-8 (IL-8) in malaria are inconsistent and unclear. This study synthesised evidence for differences in IL-8 levels in patients with malaria of various levels of severity. Relevant studies were searched in Scopus, MEDLINE, Embase, CENTRAL and PubMed from inception to 22 April 2022. Pooled mean differences (MDs) and 95% confidence intervals (CIs) were estimated using the random effects model. Of 1083 articles retrieved from the databases, 34 were included for syntheses. The meta-analysis revealed increased IL-8 levels in individuals with uncomplicated malaria compared with those without malaria (P = 0.04; MD, 25.57 pg/mL; 95% CI, 1.70 to 49.43 pg/mL; I2, 99.53, 4 studies; 400 uncomplicated malaria, 204 uninfected controls). The meta-analysis revealed comparable levels of IL-8 between the two groups (P = 0.10; MD, 74.46 pg/mL; 95% CI, -15.08 to 164.0 pg/mL; I2, 9.03; 4 studies; 133 severe malaria cases, 568 uncomplicated malaria cases). The study found evidence of increased IL-8 levels in individuals with malaria compared with those without malaria. However, no differences were found in IL-8 levels between patients with severe and non-severe malaria. Further research is needed to investigate the IL-8 cytokine levels in patients with malaria of different levels of severity.


Phylogenetics, biogeography, and staminal evolution in the tribe Mentheae (Lamiaceae).
The mint family (Lamiaceae) is the sixth largest family of flowering plants, with the tribe Mentheae containing about a third of the species. We present a detailed perspective on the evolution of the tribe Mentheae based on a phylogenetic analysis of cpDNA and nrDNA that is the most comprehensive to date, a biogeographic set of analyses using a fossil-calibrated chronogram, and an examination of staminal evolution. Data from four cpDNA and two nrDNA markers representing all extant genera within the tribe Mentheae were analyzed using the programs BEAST, Lagrange, S-DIVA, and BayesTraits. BEAST was used to simultaneously estimate phylogeny and divergence times, Lagrange and S-DIVA were used for biogeographical reconstruction, and BayesTraits was used to infer staminal evolution within the tribe. Currently accepted subtribal delimitations are shown to be invalid and are updated. The Mentheae and all five of its subtribes have a Mediterranean origin and have dispersed to the New World multiple times. The vast majority of New World species of subtribe Menthinae are the product of a single dispersal event in the mid-late Miocene. At least four transitions from four stamens to two stamens have occurred within Mentheae, once in the subtribe Salviinae, once in the subtribe Lycopinae, and at least twice in the subtribe Menthinae. Worldwide cooling trends probably played a large role in the diversification and present day distribution of the tribe Mentheae. Additional work is needed to ascertain relationships within some Mentheae genera, especially in the subtribe Menthinae.


The population requirement for cataract extraction: a cross-sectional study.
To examine the distribution in the population of indications for cataract extraction in order to relate demand for this procedure to the capacity for satisfying it. An age-stratified random population sample of 2783 individuals aged 55 years and over was taken from inner-city, urban and rural areas of Avon and Somerset. The requirement for cataract extraction was estimated on the basis of measures of vision-related quality of life, refracted visual acuity, and application of the Oxford Clinical Cataract Classification and Grading System. Data were also collected concerning suitability for surgery, including relative contraindications to surgery and whether participants considered their eyesight bad enough to merit surgery. Three sets of composite indications were defined. Estimated prevalent requirements for cataract extraction for the three sets of composite criteria were: 29 per 1000 aged over 55 years (95% CI 20-41) for the most inclusive criterion; 17 per thousand (95% CI 10-27) for the intermediate criterion; and 7 per thousand (95% CI 3-14) for the most stringent criterion. These rates are equivalent to a national prevalent requirement for England of 384,000 for the most inclusive criterion. If the approximately 15% of individuals whose desire or fitness for surgery was questionable are removed from this estimate, the prevalent requirement, including the backlog from previous unsatisfied demand, becomes 325,000 individuals. The findings suggest only a modest imbalance between supply and demand for cataract surgery. In particular there was a very small prevalence of untreated severe cataract, less than the annual health service surgical capacity, suggesting that the current National Health Service surgical capacity is adequate for cases of severe cataract.


Essential familial myoclonus.
From a family with essential familial myoclonus, 150 members in eight generations were studied. Twenty-five of them suffered from myoclonus of varying severity. The findings in routine examinations of blood, urine and cerebrospinal fluid, EEG and skull radiographs were normal. Therapeutic trials did not produce lasting satisfactory results. The most promising results were obtained with 5-hydroxytryptophan therapy. Haloperidol worsened the symptoms, while alcohol produced a striking improvement. It is suggested that serotoninergic neurons in the brain could be involved in the triggering of essential myoclonus.


Heart and lung grafts harvested en bloc: operative technique, utilization, and results.
Combined heart and lung transplantation has been shown to provide successful therapy for patients with end-stage heart and lung disease. The improved success of lung transplantation has resulted in increasing number of potential recipients and longer waiting times. Maximal utilization of all three thoracic organs is no longer a casual goal but of utmost necessity. We devised a new technique that improves operative visualization, decreases dissection time, and ensures excellent preservation of all three thoracic organs. Bench dissection after extraction of this heart-lung block allows the thoracic and cardiac surgeons to agree on precise dissection of the left atrium and adequate pulmonary venous and atrial cuff. This technique has been used in 48 of our last 50 harvests with excellent results. Utilization of heart and lungs has been 93% and 74%, respectively.


Amperometric L-lactate biosensor based on screen-printed carbon electrode containing cobalt phthalocyanine, coated with lactate oxidase-mesoporous silica conjugate layer.
A novel amperometric biosensor for the measurement of L-lactate has been developed. The device comprises a screen-printed carbon electrode containing cobalt phthalocyanine (CoPC-SPCE), coated with lactate oxidase (LOD) that is immobilized in mesoporous silica (FSM8.0) using a polymer matrix of denatured polyvinyl alcohol; a Nafion layer on the electrode surface acts as a barrier to interferents. The sampling unit attached to the SPCE requires only a small sample volume of 100 μL for each measurement. The measurement of l-lactate is based on the signal produced by hydrogen peroxide, the product of the enzymatic reaction. The behavior of the biosensor, LOD-FSM8.0/Naf/CoPC-SPCE, was examined in terms of pH, applied potential, sensitivity and operational range, selectivity, and storage stability. The sensor showed an optimum response at a pH of 7.4 and an applied potential of +450 mV. The determination range and the response time for L-lactate were 18.3 μM to 1.5 mM and approximately 90s, respectively. In addition, the sensor exhibited high selectivity for L-lactate and was quite stable in storage, showing no noticeable change in its initial response after being stored for over 9 months. These results indicate that our method provides a simple, cost-effective, high-performance biosensor for l-lactate.


GAVISUNK: genome assembly validation via inter-SUNK distances in Oxford Nanopore reads.
Highly contiguous de novo phased diploid genome assemblies are now feasible for large numbers of species and individuals. Methods are needed to validate assembly accuracy and detect misassemblies with orthologous sequencing data to allow for confident downstream analyses. We developed GAVISUNK, an open-source pipeline that detects misassemblies and produces a set of reliable regions genome-wide by assessing concordance of distances between unique k-mers in Pacific Biosciences high-fidelity assemblies and raw Oxford Nanopore Technologies reads. GAVISUNK is available at https://github.com/pdishuck/GAVISUNK. Supplementary data are available at Bioinformatics online.


Epigenetic modification and imprinting of the mammalian genome during development.
Genomic imprinting in mammals results in the differential expression of maternal and paternal alleles of certain genes. Recent observations have revealed that the regulation of imprinted genes is only partially determined by epigenetic modifications imposed on the two parental genomes during gametogenesis. Additional modifications mediated by factors in the ooplasm, early embryo, or developing embryonic tissues appear to be involved in establishing monoallelic expression for a majority of imprinted genes. As a result, genomic imprinting effects may be manifested in a stage-specific or cell type-specific manner. The developmental aspects of imprinting are reviewed here, and the available molecular data that address the mechanism of allele silencing for three specific imprinted gene domains are considered within the context of explaining how the imprinted gene silencing may be controlled developmentally.


Phonation Analysis Combined with 3D Reconstruction of the Thyroarytenoid Muscle in Aged Ovine Ex Vivo Larynx Models.
The aim of the study was to establish a basic data set of combined functional and anatomical measures of aged sheep larynges using ex vivo models. Combining these two approaches in one and the same larynx is an unmet goal so far yet is important as newer treatment strategies aim to preserve the organ structure and new assessment tools are required. Ovine larynges were used as their dimensions, and muscle fiber type distribution highly resemble the human larynx. Ex vivo animal study. Larynges of six sheep (~9 years of age) were subjected to ex vivo functional phonatory experiments. Phonatory characteristics were analyzed as a function of longitudinal vocal fold (VF) prestress. Anatomical measurements of the same larynges comprised micro-computed tomography scans followed by three-dimensional (3D) reconstructions. Using specially adapted radiological scan protocols with subsequent 3D reconstruction, muscle volumes, surface areas, and anatomical measurements were computed. Increasing longitudinal prestress yielded higher subglottal pressure (PS) for the same airflow. Quantitative differences to previous studies-such as the increased PS and increased phonation threshold pressure-were detected. We achieved excellent visualization of the laryngeal muscles and framework, resulting in accurate 3D reconstructions for quantitative analysis. We found no significant intraindividual volume differences of the thyroarytenoid muscles. The established protocol allows precise functional and anatomical measures. The data created provide a reference data set for upcoming therapeutic strategies (eg, growth factor therapy, functional electrical stimulation) that target essential structures of the VFs such as the laryngeal muscles and/or the VF mucosa.


Application of portable online LED UV fluorescence sensor to predict the degradation of dissolved organic matter and trace organic contaminants during ozonation.
This work aims to correlate signals of LED UV/fluorescence sensor with the degradation of dissolved organic matter (DOM) and trace-level organic contaminants (TOrCs) during ozonation process. Six sets of bench-scale ozonation kinetic experiments incorporated with three different water matrices and 14 TOrCs of different reactivity (group I ∼ V) were conducted. Calibrated by tryptophan and humic substances standards and verified by the lab benchtop spectroscopy, the newly developed portable/online LED sensor, which measures the UV280 absorbance, protein-like and humic-like fluorescence simultaneously, was feasible to monitor chromophores and fluorophores with good sensitivity and accuracy. The liquid chromatography with organic carbon detector combined with 2D synchronous correlation analysis further demonstrated how the DOM components of large molecular weight were transformed into small moieties as a function of the decrease of humic-like fluorescence. For TOrCs, their removal rates were well correlated with the decrease of the LED UV/fluorescence signals, and their elimination patterns were mainly determined by their reactivity with O3 and hydroxyl radicals. At approximately 50% reduction of humic-like fluorescence almost complete oxidation of TOrCs of group I and II was reached, a similar removal percentage (25-75%) of TOrCs of group III and IV, and a poor removal percentage (<25%) of group V. This study might contribute to the smart control of advanced oxidation processes for the water and wastewater treatment in the future.


Risk indicators for cesarean section due to cephalopelvic disproportion in Lamphun hospital.
To investigate risk indicators for cesarean section due to cephalopelvic disproportion. Department of Obstetrics & Gynecology, Lamphun Hospital. Case-control study. Cases were 87 pregnant women delivered by cesarean section due to cephalopelvic disproportion at Lamphun Hospital between October 1st, 2003 and June 30th, 2004. Controls were 113 pregnant women delivered by normal labour during the same period. Maternal age, gravidity, parity, maternal height, pre-pregnancy weight, gestational age, weight before delivery, weight gain, symphysis-fundal height, birthweight and newborn gender were mainly focused. Information were obtained from medical records. Groups were compared by t-test and exact probability test as appropriate. Risk indicators were analyzed by odds ratio from univariable and multiviariable logistic regression. Risk indicators significantly associated with cesarean section due to cephalopelvic disproportion included symphysis-fundal height greater than 35 cm. (OR = 9.38, 95% CI = 3.42-25.73); nulliparity (OR = 5.36, 95%CI = 2.24-12.82); maternal height less than 152 cm. (OR = 3.65, 95%CI = 1.63-8.17) and weight gain more than 15 kg. (OR = 2.67, 95%C1 = 1.32-5.39). Risk factors for cesarean section due to cephalopelvic disproportion included symphysis-fundal height greater than 35 cm, nulliparity, maternal height less than 152 cm. and weight gain more than 15 kg. Early detection of these risk indicators before delivery helps obstetricians and nurses to recognize potential obstructed labor and prepare for safe delivery in advance.


Intraspecific variation among Chinook Salmon populations indicates physiological adaptation to local environmental conditions.
Understanding interpopulation variation is important to predicting species responses to climate change. Recent research has revealed interpopulation variation among several species of Pacific salmonids; however, the environmental drivers of population differences remain elusive. We tested for local adaptation and countergradient variation by assessing interpopulation variation among six populations of fall-run Chinook Salmon from the western United States. Juvenile fish were reared at three temperatures (11, 16 and 20°C), and five physiological metrics were measured (routine and maximum metabolic rate, aerobic scope, growth rate and critical thermal maximum). We then tested associations between these physiological metrics and 15 environmental characteristics (e.g. rearing temperature, latitude, migration distance, etc.). Statistical associations between the five physiological metrics and 15 environmental characteristics supported our hypotheses of local adaptation. Notably, latitude was a poor predictor of population physiology. Instead, our results demonstrate that populations from warmer habitats exhibit higher thermal tolerance (i.e. critical thermal maxima), faster growth when warm acclimated and greater aerobic capacity at high temperatures. Additionally, populations with longer migrations exhibit higher metabolic capacity. However, overall metabolic capacity declined with warm acclimation, indicating that future climate change may reduce metabolic capacity, negatively affecting long-migrating populations. Linking physiological traits to environmental characteristics enables flexible, population-specific management of disparate populations in response to local conditions.


Effects of temperature and time on mutagen formation in pan-fried hamburger.
Mutagenic activity generated in hamburger during pan-frying is dependent upon both temperature and time, with temperature appearing to be the more important variable. Uniformly prepared frozen hamburger pattie (115 g; 19% fat) were fried under carefully controlled conditions at 143 degrees C, 191 degrees C and 210 degrees C. Mutagenic activity assayed with the Ames test was not detected in uncooked hamburger, and in hamburger fried at 143 degrees C mutagenic activity remained low at all times studied (4--20 min). In contrast, frying at 191 degrees C or 210 degrees C for up to 10 min resulted in the generation of considerably higher levels of mutagenic activity. Mutagenic activity in fried hamburgers sold at selected restaurants ranged from very low to moderately high. Evidence is also presented for mutagenic inhibitory activity in uncooked and fried hamburger. Mutagenic inhibitory activity decreased mutagenesis mediated by liver S-9 from normal rats but not from Aroclor 1254-treated rats.


Role of survivin as prognostic and clinicopathological marker in gastric cancer: a meta-analysis.
Survivin has been implicated as a potential prognostic marker in a wide range of malignant tumours. However, the prognostic impact of survivin in gastric cancer remains to be controversial and published data are sometimes heterogeneous. Thus, aim of this study was to review the literature by performing an electronical database search via PubMed and EMBASE to identify eligible studies that assessed the impact of survivin as prognostic marker and its association with clinicopathological variables. Database search until November 21st 2012 retrieved 20 studies comprising 2,695 gastric cancer patients that assessed expression of survivin by immunohistochemistry or RT-PCR analyses in gastric cancer specimens. Meta-analyses of clinicopathological variables revealed an association between the expression of survivin and the presence of lymph node metastases (pooled OR: 0.58; 95 % CI 0.35-0.96). In addition, a correlation between the expression of survivin and overall survival for patients with gastric cancer (pooled HR 1.93; 95 % CI 1.51-2.48) became evident. More importantly, we were able to exclude a severe heterogeneity (I(2) = 31 %) or publication bias for the survival analyses. Furthermore, one-way sensitivity analysis and subgroup analyses regarding the method used to detect survivin, the type of survival analysis, the study quality and whether information was provided regarding neoadjuvant therapy supported our initial results. In conclusion, this meta-analysis indicates the prognostic significance of survivin in patients with gastric cancer.


Acellular Dermal Matrix Tissues in Genitourinary Reconstructive Surgery: A Review of the Literature and Case Discussions.
There have been major advancements in the field of urologic reconstruction and gender-affirming surgeries over the past 10 years. These operations have become increasingly complex involving multiple revisions, with limited healthy native tissue availability. Grafts are frequently needed when a patient's own tissue is expected to have poor wound-healing properties. To reduce the morbidity associated with autologous grafts and complications associated with synthetic grafts, acellular dermal matrices (ADMs) can be used as substitutes in genitourinary surgery as they demonstrate decreased immunogenicity and retaine structural integrity. The purpose of this review is to describe the importance and potential uses of ADMs by reviewing the literature and highlighting key examples of our institution's expanded application of ADM grafts in genitourinary reconstruction. We performed a literature review for the use of ADMs in genitourinary surgery including the search terms acellular dermal matrix, alloderm, extracellular matrix, penis, penile reconstruction, intrapenile prosthesis, phalloplasty, neophallus, urethroplasty, artificial urinary sphincters, Peyronie's disease, and urology. We highlight 5 representative genitourinary reconstructive cases performed at this institution where ADMs contributed to surgical success. Genitourinary reconstructive surgeries that have used ADMs in the literature included neophallus construction for gender affirmation, phalloplasty for trauma, penile augmentation, and plaque excision and grafting for Peyronie's disease. Biomechanical studies across different graft types are limited in genitourinary applications. Initial studies using ADMs indicate benefits of limited inflammatory response, finite elasticity, and substantial tensile strength, acceptably mimicking properties of the native tissue. Our experience and the current literature suggest that human ADM is a valuable option for tunica albuginea replacement, but its use to support free grafts should be cautioned secondary to graft take. Haney NM, Huang MM, Liu JL, et al. Acellular Dermal Matrix Tissues in Genitourinary Reconstructive Surgery: A Review of the Literature and Case Discussions. Sex Med Rev 2021;9;488-497.


Follow up study on children with dyslipidaemia detected by mass screening at 18 months of age: effect of 12 months dietary treatment.
The present study was done to evaluate the effect of short-term dietary therapy on 148 dyslipidaemic children (24 familial hypercholesterolaemia, 105 non-familial hypercholesterolaemia and 19 hypertriglyceridaemia), detected by mass screening in children at 18 months of age. In the model diet used for treatment, 15% of the total calories were obtained from protein, 27% from fat and 57% from carbohydrate. Cholesterol intake was set at < 200 mg/day and the ratio of polyunsaturated to saturated fatty acid (P/S ratio) was 1.2. When compared to the composition of the diet ingested by the dyslipidaemic children, only the P/S ratio changed from 0.7 to 1.2. During 12 months treatment, levels of total cholesterol, low density lipoproteins cholesterol and apoB decreased by 10%-15% in children with familial and non-familial hypercholesterolaemia. There was no significant change in the levels of high density lipoproteins. In 19 children with hypertriglyceridaemia, the intake of carbohydrate was limited to 55% of the total calories consumed and after 12 months of treatment, triglyceride levels reverted to normal. Throughout the study period, approximately 70% of the children on this dietary therapy were seen in our clinics every 3-6 months and physical development was within normal ranges. These results, taken together, indicate that dietary therapy can be effective for correcting dyslipidaemia, even in young children.


DRD4 48 bp VNTR but not 5-HT 2C Cys23Ser receptor polymorphism is related to antipsychotic-induced weight gain.
Weight gain is a major side effect of antipsychotic treatment. The antidopaminergic and antiserotonergic effect of antipsychotics may contribute to antipsychotic-induced weight gain. We, therefore conducted a prospective clinical study, to investigate whether the D4 receptor (DRD4) 48 bp (base pair) variable number of tandem repeat (VNTR) polymorphism and the 5-hydroxytryptamine 2C receptor (HT(2C)) cysteine for serine substitution at position 23 (Cys23Ser) polymorphism may influence weight gain during antipsychotic treatment in a naturalistic setting of 102 Caucasian psychiatric in-patients. Patients suffering from psychotic disorders and treated according to local clinical practice were classified as either homozygous for the shorter alleles of the DRD4 48 bp VNTR polymorphism (<7-fold repeat, group 1) or heterozygous/homozygous for the long allele (7-fold repeat or higher, group 2). HT(2C) Cys23Ser polymorphism male patients were grouped hemizygous G (Cys) or C (Ser), while female patients were GG, GC or CC and both sexes were evaluated separately. Concerning the DRD4 48 bp VNTR polymorphism the increase in body mass index was significantly less in group 1 (0.38 kg m(-2); s.d.=1.04) than in group 2 (0.89 kg m(-2); s.d.=1.23; P=0.003). The difference between the genotype groups remained significant in male patients but not in female patients. In contrast, no influence on antipsychotic-induced increase in body weight was observed for the HT(2C) Cys23Ser polymorphism. These results support the hypothesis that the DRD4 48 bp VNTR polymorphism influences antipsychotic-induced weight gain. Male patients may be more affected than female patients. Due to the limitations of the study (heterogeneity of treatment, pretreatment and concomitant therapy) further studies are required before diagnostic genotyping of the DRD4 48 bp VNTR polymorphism may be useful for individualizing therapy.


Vulnerability and revictimization: Victim characteristics in a Dutch assault center.
Sexual and family violence are highly prevalent problems with numerous negative health consequences. Assault centres, such as the Centre for Sexual and Family Violence (CSFV) in the Netherlands, have been set up to provide optimal care to victims. We wanted to gain insight into characteristics of the population that presented to the Centre in order to customize care to their needs. File analysis was conducted of victims who attended the CSFV between 2013 and 2016. Data were analyzed in SPSS. A total of 121 victims entered the Centre, 93% of them being female. Forty-two per cent were adult victims of sexual violence, 28% minor victims of sexual violence and 30% adult victims of family violence. One-third of sexual and two-third of family violence victims had experienced prior abuse. Current use of psychosocial services and psychiatric medication was high, and a cognitive disability was present in 18% of the sexual violence victims. Half the victims reported, but when the perpetrator was a recent contact, e.g., someone met at a party, reporting rates went down. Sexual and family violence victims share characteristics that indicate vulnerability, suggesting that care for both groups might best be combined in one single assault centre. In this way, victims can make use of the same services and knowledge of gender-based violence. One of the major aims of assault centres is to provide psychosocial follow-up care and facilities for reporting. The victims' needs in these matters deserve further research.


Biaryl diamides as potent melanin concentrating hormone receptor 1 antagonists.
Herein, we report the discovery of the potent and selective biaryl diamide derived MCH-R1 receptor antagonist 1, which was identified upon modification of a previously disclosed biaryl urea series. This paper describes one of the strategies incorporated to remove the highly mutagenic biarylaniline present in an otherwise promising biaryl urea series.


Ketamine vs midazolam: Mood improvement reduces suicidal ideation in depression.
Studies demonstrate rapid antidepressant and anti-suicidal ideation effects of subanesthetic ketamine. The specific subcomponents of depression that are most closely tied to reduction of suicidal ideation with ketamine treatment are less explored. Exploratory, post hoc analysis of data from a randomized clinical trial of ketamine vs midazolam in patients with major depressive disorder (MDD) and clinically significant suicidal ideation examined changes in factor analysis-derived symptom clusters from standard measures of depression (Hamilton Depression Rating Scale, HDRS; Beck Depression Inventory, BDI) and mood disturbance (Profile of Mood States, POMS), and their relationship to severity of suicidal ideation (Beck Scale for Suicidal Ideation; SSI). Ratings obtained before and one day after blinded intravenous infusion were decomposed into component factors or published subscales. Treatment effects on factors/subscales were compared between drugs, correlations with changes in suicidal ideation were tested, and stepwise regression was used to derive predictors of change in SSI. Factor scores for HDRS Psychic Depression, HDRS Anxiety, BDI Subjective Depression, POMS Depression and POMS Fatigue improved more with ketamine than midazolam. Stepwise regression showed across both drugs that improvement in HDRS Psychic Depression, POMS Depression, and HDRS Anxiety predicted 51.6% of the variance in reduction of suicidal ideation. Secondary analysis of clinical trial data. Ketamine's rapid effects on suicidal ideation appear to be mostly a function of its effects on core mood and anxiety symptoms of MDD, with comparatively little contribution from neurovegetative symptoms with the potential exception of vigor/fatigue. Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT01700829.


Seasonal changes of the ovarian atretic follicles of the ground squirrel (Citellus citellus L.).
The ovaries of 84 ground squirrels (C. Citellus L.) were studied during the four seasons of the year. The ovarian atretic follicles were examined by histological methods and by electron microscopy. The histoenzyme activities of NAD.H2-tetrazolium reductase, glucose-6-phosphate dehydrogenase, and 3 beta-hydroxy-delta 5-steroid dehydrogenase were photometrically demonstrated. The steroid-producing atretic follicles were mainly described as they reached their highest enzyme activity during the lactation period in April. The atresia of the primordial and primary follicles was manifested by disappearance of the oocyte and preservation of the granulose cells surrounded by basal lamina. Atresia of follicles with two oocytes was a typical process for the ground squirrel. Later on the oocytes and the granulose cells around it disappeared. The remaining part of the follicle continued its development and reached maturity. Atresia was observed mainly in March, April, and May.


Effects on respiration of CPAP immediately after extubation in the very preterm infant.
The effects of continuous positive airway pressure (CPAP) on pulmonary function during weaning from ventilator treatment were examined immediately after extubation in 17 very preterm infants, who had been ventilator-treated because of hyaline membrane disease (15 infants) and chronic pulmonary insufficiency of prematurity (two infants). Seven infants had bronchopulmonary dysplasia. Median birthweight was 920 g and median gestational age 26 completed weeks. The median duration of ventilator treatment was 10 days. Application of CPAP by means of a face chamber device after endotracheal extubation significantly lowered the frequency of apnea (P = 0.02) and enhanced oxygenation (P = 0.001). The respiratory mechanical indices derived from flow rate and juxta-diaphragmatic esophageal pressure measurements showed a reduced elastic (P = 0.03) and resistive (P = 0.02) load on the diaphragm. Even if the measured values do not accurately represent absolute resistances and compliances, the relative values of end-inspiratory and end-expiratory pressures differed significantly with and without CPAP (P = 0.001 and 0.002, respectively). We found CPAP applied via the face chamber technique immediately after extubation to be beneficial and to facilitate weaning from ventilator treatment in very preterm infants.


Effects of glucose transport on the incorporation of 32P-inorganic phosphate into phospholipids in Hymenolepis diminuta (Cestoda).
1. The absorption of glucose and alpha-methyl-D-glucoside by Hymenolepis diminuta was concentration dependent. 2. alpha-Methyl-D-glucoside competitively inhibited glucose absorption and was not metabolised by the parasite. 3. alpha-Methyl-D-glucoside significantly lowered (P less than 0.05) the incorporation of 32Pi into all phospholipid classes. 4. Glucose inhibited (P less than 0.01) 32Pi incorporation into phosphatidylcholine only. 5. Phlorizin did not affect 32Pi labelling of phospholipids. 6. Serotonin and histamine stimulated (P less than 0.01) 32Pi labelling of all phospholipid classes. 7. Radioactivities in water soluble fractions were increased (P less than 0.01) in the presence of glucose, serotonin and histamine.


Partnerships with health and private voluntary organizations: what are the issues for health authorities and boards?
The number of voluntary organizations active in health care is considerable. There have been recent calls for a new closer working relationship between voluntary bodies and the National Health Service. The relationship between the two healthcare sectors needs to be efficient and harmonious in the interests of patient care; however, little is known about the nature and problems in the current relationship. The present study was undertaken to examine aspects of this relationship from the point of view of health board personnel. To identify the practices and views of Scottish health board staff concerning the funding, role and responsibility of voluntary organizations in the health sector. A qualitative study based on in-depth interviews with health board officials in all 15 Scottish health boards. Policies for financial and other relationships with the voluntary sector were often not explicit. The levels and method of funding voluntary health organizations varied across boards, as did the tenure of awards (from 1 to 3 years). Demand for funding far exceeded monies available. Some health boards ensured accountability through audited accounts, annual reports and site visits; however, others thought this inappropriate for small organizations. Health boards recognized the problems of the precariousness of funding and the administrative burden of the monitoring process and the ritual of applying for funding. The uncertainties of long-term funding may impede the contribution of voluntary organizations. There is a tension between the requirements of clinical governance and the ability of small voluntary organizations to provide the necessary documentation. One proposed solution, to reduce the number of organizations, might not appeal to the voluntary sector. Future initiatives could address the problem of tailoring funding and accounting to the resources of voluntary organizations.


Polysaccharides improved the viscoelasticity, microstructure, and physical stability of ovalbumin-ferulic acid complex stabilized emulsion.
This study explored the mechanism underlying the interactions between polysaccharides and ovalbumin-ferulic acid (OVA-FA) and the effect of polysaccharides on OVA-FA-stabilized emulsions. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used to study the polysaccharide OVA-FA interactions mechanism and to resolve the changes in the protein secondary structure and crystal structure. OVA-FA-polysaccharide-stabilized emulsions were studied using confocal laser scanning microscopy (CLSM), and their rheological properties and stability were determined. The results showed that the non-covalent interactions between polysaccharides and OVA-FA led to an increase in the β-sheet content of OVA and a decrease in the α-helix and random coil contents. The stability of the OVA-FA-polysaccharide-stabilized emulsions was better compared with that of the OVA-FA-stabilized emulsions. By comparing the different OVA-FA-polysaccharide-stabilized emulsions, we observed that OVA-FA-agar did not stabilize the emulsion well, while the OVA-FA-SA- and OVA-FA-KC-stabilized emulsions had good elasticity, and the microstructure and storage stability of the OVA-FA-KC-stabilized emulsion were better. Our findings provide a new perspective for the application of OVA-FA-KC in complex food emulsions.


Two dimensionality of the correspondence process in apparent motion.
A fundamental process underlying motion perception is the matching of corresponding elements in different views. In this correspondence process spatial separation between elements plays a major role. The relevant separation is shown by the current study to be the two-dimensional, uninterpreted distance, a finding that has an implication to the level at which the correspondence process is carried out. The current findings are compared with earlier results concerning 'optimality' of apparent motion to conclude that optimality cannot serve as a measure for the correspondence strength.


Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids.
An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo®; Myfembree®) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids.


Color of Colon Content of Normal and Intrauterine Growth-Restricted Weaned Piglets is Associated with Specific Microbial Taxa and Physiological Parameters.
A well-balanced gut microbiome is associated with improved health outcomes, but to date, the GM of IUGR piglets have only been sparsely investigated. Here, we investigated GM composition, color of colon content, and blood parameters of 20 IUGR and 20 normal 24-day-old piglets. No significant differences were detected in colon microbiota composition between IUGR and the normal piglets with respect to alpha and beta diversity measures. The colon content of these piglets displayed three colors: brown, black, and yellow. Interestingly, the color of the colon content varied with microbial community composition, with significant differences in the relative abundance of taxa belonging to Fusobacteria and Treponema. Fusobacteria were most abundant in yellow fecal samples, with a mean relative abundance around 5.6%, whereas this was 0.51% within brown and 0.02% for the black fecal samples. Fusobacteria positively correlated with total blood protein, albumin, and triglycerides. Contrarily, Treponema was at 0.9% the most abundant in black fecal samples, while present at 0.1% of relative abundance in brown fecal samples and 0.01% in yellow samples, correlating positively with blood iron content. This study indicates that colon/fecal content color can be used as indicator for specific GM and metabolite signatures.


[Expression of mitosis checkpoint gene CHFR in acute leukemia].
To investigate the expression of mitosis checkpoint gene CHFR in adult patients with acute leukemia (AL) and its clinical significance. Four ml of bone marrow was extracted from 65 AL patients, 38 males and 27 females, with the median age of 35, 43 with acute myelocytic leukemia (AML) and 22 with acute lymphocytic leukemia (ALL), 45 de novo patients and 20 recurrent patients, and 8 normal donor of allogeneic bone marrow transplantation as controls. The bone marrow mononuclear cells (BMNC) were isolated. The cell cycle was examined by flow cytometric analysis. The CHFR mRNA level in the BMNC was measured by RT-PCR. The expression of CHFR protein was detected by Western blotting in 32 of the 65 patients and 8 normal persons as control. (1) The levels of CHFR protein and mRNA were correlated with the cumulative percentages of cells in S phases. (2) The expression level of CHFR protein in 40.6% (13/32) of the AL patients and that of the CHFR mRNA in 60.0% (27/45) of the AL patients were both significantly lower than those of the normal controls. (3) The mean expression level of CHFR protein in the recurrent acute lymphoblastic leukemia (ALL) was 0.71, significantly higher than that of the de novo group (0.38, t = 2.54, P = 0.017). (4) The complete remission (CR) rates in the AL patients with high expression levels of CHFR protein and mRNA were 30.2% and 42.4% respectively, significantly lower than those in the AL patients with low expression levels (88.6% and 85.4% respectively, both P < 0.05). Multivariate analysis showed that CHFR was one of the influencing factors of CR rate of AL patients. By affecting mitotic checkpoint function, CHFR inactivation plays a key role in tumorigenesis in adult patients with acute leukemia. Moreover, the aberrant expression of CHFR appears to be a good molecular marker to predict the sensitivity of acute leukemia to chemotherapy.