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The optimal treatment algorithm for patients with degenerative lumbar spondylolisthesis has not been clarified. Part of the reason for this is that the natural history of degenerative spondylolisthesis (DS) has not been sufficiently studied. Comprehension of the natural history is essential for surgical decision making. We aimed to determine 1) the proportion of patients that develop de novo DS during follow-up; and 2) the proportion of patients with progression of preexistent DS by conducting a systematic review and meta-analysis of the literature. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Ovid, EMBASE, and the Cochrane Library were searched from their inception through April 2022. Demographic values of the study populations, grade of slip, rate of slippage before and after the follow-up period, and percentage of patients with slip in the populations at baseline and after follow-up were the extracted parameters. Of the 1909 screened records, eventually 10 studies were included. Of these studies, 5 reported the development of de novo DS and 9 reported on the progression of preexistent DS. Proportions of patients developing de novo DS ranged from 12% to 20% over a period ranging from 4 to 25 years. The proportion of patients with progression of DS ranged from 12% to 34% over a period ranging from 4 to 25 years. Systematic review and metanalysis of DS on the basis of radiologic parameters revealed both an increasing incidence over time and an increasing progression of the slip rate in up to a third of the patients older than 25 years, which is important for counseling patients and surgical decision making. Importantly, two thirds of patients did not experience slip progression. [ABSTRACT FROM AUTHOR]

We aimed to determine: (1) the prevalence and socio-economic distribution of undiagnosed, untreated, and uncontrolled diabetes mellitus (DM); (2) the relationship between socio-economic status (SES) and undiagnosed, untreated, and uncontrolled DM; and (3) if this relationship is mediated by gender. Cross-sectional nationally representative household-based survey. We used data from the Bangladesh Demographic Health Survey from 2017 to 18. Our findings were based on the responses of 12,144 individuals aged 18 years and older. As a measure of SES, we focused on standard of living (hereinafter referred to as wealth). The study's outcome variables were prevalence of total (diagnosed + undiagnosed), undiagnosed, untreated, and uncontrolled DM. We used three regression-based approaches—adjusted odds ratio, relative inequality index, and slope inequality index—to assess different aspects of SES differences in the prevalence of total, undiagnosed, untreated, and uncontrolled DM. We used logistic regression analysis to look at the adjusted association between SES and the outcomes after gender stratification to see whether gender status moderates the association between SES and the targeted outcomes. In our sample analysis, the age-adjusted prevalence of total, undiagnosed, untreated, and uncontrolled DM was 9.1%, 61.4%, 64.7%, and 72.1%, respectively. Females had a higher prevalence of DM and undiagnosed, untreated, and uncontrolled DM than males. When compared to people in the poor SES group, people in the rich and middle SES groups had 2.60 times (95% confidence interval [CI] 2.05–3.29) and 1.47 times (95% CI 1.18–1.83) higher chance of developing DM. When compared to individuals in the poor SES group, those in the rich SES groups were 0.50 (95% CI 0.33–0.77) and 0.55 times (95% CI 0.36–0.85) less likely to have undiagnosed and untreated DM. In Bangladesh, rich SES groups were more likely than poor SES groups to have DM, whereas poor SES groups with DM were less likely than rich SES groups to be aware of their disease and obtain treatment. The government and other concerned parties are urged by this study to pay more attention to developing suitable policy measures to reduce the risk of DM, particularly among rich SES groups, as well as targeted efforts to screen for and diagnose DM in socio-economically disadvantaged groups. [ABSTRACT FROM AUTHOR]

Glaucoma is a chronic, progressive disease leading to irreversible blindness if left untreated; however, since reducing intraocular pressure has proven to be successful in slowing disease progression, little is known about the natural history of untreated glaucoma. This knowledge can be valuable in guiding management decisions in the era of personalized medicine. A systematic search was performed in Medline (PubMed), Embase, and Web of Science in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRIMSA) guidelines. The rate of structural and/or functional progression and conversion to glaucoma or to a more advanced stage of glaucoma are discussed for ocular hypertension and different types of open-angle glaucoma. Forty-three studies were included. Different rates of progression were found both among and within the different diagnostic groups that belong to the open-angle glaucoma spectrum. The highest rate was found in pseudoexfoliation glaucoma, followed by high tension glaucoma, normal tension glaucoma, and ocular hypertension, in decreasing order. The lowest rate was observed in glaucoma suspects. The known rates of progression provide valuable prognostic information for ophthalmologists and patients. Nonetheless, due to high variability among patients, individual progression cannot be accurately predicted and repeated follow-up examinations are required to estimate individual progression. [ABSTRACT FROM AUTHOR]

Background: There is limited research examining the natural trajectories of depression and anxiety, how these trajectories relate to baseline neural circuit function, and how symptom trajectory-circuit relationships are impacted by engagement in lifestyle activities including exercise, hobbies, and social interactions. To address these gaps, we assessed these relations over three months in untreated participants.Methods: 262 adults (59.5% female, mean age 35) with symptoms of anxiety and depression, untreated with pharmacotherapy or behavioral therapy, completed the DASS-42, WHOQOL, and custom surveys at baseline and follow-up to assess symptoms, psychosocial function, and lifestyle activity engagement. At baseline, participants underwent fMRI under task-free and task-evoked conditions. We quantified six circuits implicated in these symptoms: default mode, salience, negative and positive affect, attention, and cognitive control.Results: From baseline to 3 months, some participants demonstrated a natural improvement in anxiety (24%) and depression (26%) symptoms. Greater baseline salience circuit connectivity (pFDR=0.045), specifically between the left and right insula (pFDR=0.045), and greater negative affect circuit connectivity elicited by sad faces (pFDR=0.030) were associated with anxiety symptom improvement. While engagement in lifestyle activities were not associated with anxiety improvements, engagement in hobbies moderated the association between negative affect circuit connectivity and anxiety symptom improvement (p = 0.048).Limitations: The observational design limits causal inference.Conclusions: Our findings highlight the role of the salience and negative affect circuits as potential circuit markers of natural anxiety symptom improvements over time. Future studies that identify biomarkers associated with symptom improvements are critical for the development of personalized treatment targets. [ABSTRACT FROM AUTHOR]

Background: Comparing the course of antipsychotic-naïve psychosis in low- and middle-income countries (LMIC) may help to illuminate core pathophysiologies associated with this condition. Previous reviews-primarily from high-income countries (HIC)-identified cognitive deficits in antipsychotic-naïve, first-episode psychosis, but did not examine whether individuals with psychosis with longer duration of untreated psychosis (DUP > 5 years) were included, nor whether LMIC were broadly represented.Method: A comprehensive search of PUBMED from January 2002-August 2018 identified 36 studies that compared cognitive functioning in antipsychotic-naïve individuals with psychosis (IWP) and healthy controls, 20 from HIC and 16 from LMIC.Results: A key gap was identified in that LMIC study samples were primarily shorter DUP (<5 years) and were primarily conducted in urban China. Most studies matched cases and controls for age and gender but only 9 (24%) had sufficient statistical power for cognitive comparisons. Compared with healthy controls, performance of antipsychotic-naïve IWP was significantly worse in 81.3% (230/283) of different tests of cognitive domains assessed (90.1% in LMIC [118/131] and 73.7% [112/152] in HIC).Conclusions: Most LMIC studies of cognition in antipsychotic-naïve IWP adopted standardized procedures and, like HIC studies, found broad-based impairments in cognitive functioning. However, these LMIC studies were often underpowered and primarily included samples typical of HIC: primarily male, young-adult, high-school educated IWP, in their first episode of illness with relatively short DUP (<5 years). To enhance understanding of the long-term natural course of cognitive impairments in untreated psychosis, future studies from LMIC should recruit community-dwelling IWP from rural areas where DUP may be longer. [ABSTRACT FROM AUTHOR]

Background: Obesity is up to 4 times higher in patients with schizophrenia than in the general population. However, the link between obesity and schizophrenia in the absence of antipsychotic use is unclear. Therefore, we aimed to examine differences in obesity measures (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) in antipsychotic-naive and minimally treated (up to 2 weeks of lifetime antipsychotic exposure) patients with psychosis compared to healthy controls (HCs).Methods: A systematic search was conducted using Ovid Medline®, PsycINFO, and Embase. Standardized mean differences (SMDs) in obesity measures between groups were calculated. Separate sensitivity analyses were performed to examine the effects of age, sex, and ethnicity; antipsychotic exposure; and schizophrenia-related psychosis on SMDs.Results: A total of 23 studies were included in the meta-analysis (BMI = 23, WC = 9, WHR = 5). BMI was lower (SMD = -0.19, 95% CI = -0.34 to -0.05, P = 0.009) and WHR was elevated (SMD = 0.34, 95% CI = 0.14 to 0.55, P = 0.001) in patients. These differences remained after analyses were restricted to patients matched with HCs for age, sex, and ethnicity; to antipsychotic-naive patients; and to patients with schizophrenia-related diagnoses.Conclusions: Differences in BMI and WHR were observed in never and minimally treated patients with psychosis compared to HCs. Future research is warranted to understand these alterations in the context of body fat biomarkers and neuropathology of psychiatric disorders, independent of the effects of antipsychotics. [ABSTRACT FROM AUTHOR]

Background Studies using proton magnetic resonance spectroscopy ( 1 H-MRS) have reported altered neurometabolite levels in patients with schizophrenia. However, results are possibly confounded by the influence of antipsychotic (AP). Thus, this meta-analysis aimed to examine neurometabolite levels in AP-naïve/free patients with schizophrenia. Methods A literature search was conducted using Embase, Medline, and PsycINFO to identify studies that compared neurometabolite levels in AP-naïve/free patients with schizophrenia to healthy controls (HCs). Eight neurometabolites (glutamate, glutamine, glutamate + glutamine, N -acetylaspartate [NAA], choline, creatine, myo-inositol, and γ-Aminobutyric acid [GABA]) and seven regions of interest (ROI; medial prefrontal cortex, dorsolateral prefrontal cortex, frontal white matter, occipital lobe, basal ganglia, hippocampus/medial temporal lobe, and thalamus) were examined. Results Twenty-one studies (N = 1281) were included in the analysis. The results showed lower thalamic NAA levels (3 studies, n = 174, effect size = −0.56, P = 0.0005) in the patient group. No group differences were identified for other neurometabolites. Conclusions Our findings suggest that impaired neuronal integrity in the thalamus may be a potential trait maker in the early stages of schizophrenia. [ABSTRACT FROM AUTHOR]

• The introduction of oral disease-modifying therapies (DMTs) translated to a higher rate of treatment in patients with remitting multiple sclerosis (RRMS). • In Patients with clinically isolated syndrome (CIS), there was no change in treatment rate. This could be due to limited therapeutic options in CIS. • Older age and mild course were associated with the decision against DMTs which highlights the need for guidelines in these circumstances. Several disease-modifying therapies (DMTs) show efficacy in relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS). However, there is still a relevant proportion of patients who remain untreated. We provide real-world data on untreated and treated patients and we report whether and how the introduction of oral DMTs changed the treatment decision. Furthermore, we discuss possible reasons for not receiving DMTs. We conducted a retrospective cross-sectional study and analysed demographic and clinical data of patients with RRMS and CIS at our MS center. Comparison was made between untreated and treated patients in 2010 (before the introduction of oral DMTs) and in 2014 (after the introduction of oral DMTs). Furthermore, we analysed reasons for the decision against DMTs in patients who never received DMTs and patients who discontinued DMTs. We analysed datasets of 344 MS patients in 2010 and 253 in 2014. There were more untreated patients in CIS than in RRMS. In RRMS, the proportion of untreated patients decreased significantly between 2010 and 2014 from 23.6% to 11.1%, while the use of oral medications increased significantly from <1% to more than 50% in 2014. In CIS, there was no significant change in untreated patients between 2010 and 2014 (61.1% in 2010 to 52.6% in 2014). Untreated patients with RRMS were significantly older and had lower ARR than treated patients. Patients who never received DMT had lower EDSS compared to patients that had been treated before. The main reasons for the decision against DMT were "belief in a benign course" and "fear of adverse effects". Treatment discontinuation was caused mainly by the adverse effects. In our data a relevant proportion of patients with RRMS and CIS did not receive any DMT. We hypothesize that in patients with RRMS the introduction of oral DMTs translated to a higher rate of treatment, whereas in CIS there no change was observed. This could be due to limited therapeutic options in CIS. There is more information needed regarding the treatment recommendation for older patients and patients with mild course of the disease. [ABSTRACT FROM AUTHOR]

This study evaluated impact of untreated dye effluent on heavy metal uptake by Amaranthus cruentus L. under field condition. Amaranths grown for two consecutive dry seasons were irrigated with dye effluent concentrations of 0 (control) 10, 20, 30 and 40%. Effluent concentrations were analyzed for physico-chemical and heavy metal properties. The result showed that heavy metals taken up and accumulated in amaranths tissues increased significantly ( p ≤ 0.05) with dye effluent concentration. Heavy metals accumulated more in edible shoots than roots except chromium. Bioaccumulations of heavy metals in 2012 were in several folds higher than in 2011 dry season. In the second season, regardless of effluent sources, dye concentration of 20% gave the highest accumulations of Manganese (Mn), Iron (Fe) and Zinc (Zn) in the edible shoots. The highest accumulations of heavy metals were higher than 0.3 mg kg −1 allowable limits in vegetables by Food and Agricultural Organization/World Health Organization/Federal Environmental Protection Agency. Irrigation of vegetable with untreated dye effluent should be discouraged due to potential health risks on human and general contamination of the environment. [ABSTRACT FROM AUTHOR]

Objective The aim of this study is to investigate emotional and behavioral problems among Indonesian patients with disorders of sex development (DSD) who recently came under clinical management. As diagnostic procedures and treatment had been delayed, patients progressively developed ambiguous bodies, difficult to conceal from outsiders. Method We compared 118 Indonesian patients with DSD aged 6–41 years (60 children, 24 adolescents, 34 adults) and 118 healthy control subjects matched for age, gender, and residential settings. We used the Child Behavioral Checklist (CBCL), Youth Self-Report (YSR), and Adult Self-Report (ASR) to examine differences between patient and control groups as well as differences within patients groups. Results On the CBCL, parents of young children with DSD reported significantly more emotional and behavioral problems than parents of matched control. Parents of daughters with CAH reported that their daughters withdrew themselves from social interactions. On the ASR, adults with DSD reported significantly more internalizing problems than controls, particularly anxiety and depression. No other differences in emotional functioning were found across different diagnostic groups. Conclusions Indonesian patients with DSD who were untreated for most of their lives suffered more emotional and behavioral problems than matched controls. Differences and similarities between our findings and observations in patients from Western countries will be discussed. [ABSTRACT FROM AUTHOR]

Abstract: We report on 348 patients≥70 years (median age 78 years) with acute myeloid leukemia (>50% with secondary AML) randomized to receive either 600mg or 300mg of tipifarnib orally twice daily on days 1–21 or days 1–7 and 15–21, repeated every 28 days (4 treatment regimens). Responses were seen in all regimens, with overall response rate (CR+CRi+PR) highest (20%) among patients receiving tipifarnib 300mg twice daily on days 1–21. Toxicities were acceptable. Unless predictors of response to tipifarnib are identified, further study as a single agent in this population is unwarranted. [Copyright &y& Elsevier]

The aim of the meta-analysis of randomized controlled trials (RCTs) was to compare the effectiveness of glycemic control and hypoglycemia risk of combination therapy (metformin plus a low hypoglycemic risk antidiabetic drug) vs. standard metformin monotherapy, in patients with untreated type 2 diabetes mellitus (T2DM). We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through October 31, 2021 to find relevant RCTs. Efficacy outcomes were changes in hemoglobulin A1c (HbA1c) and fast plasma glucose (FPG) from baseline as well as proportion of patients achieving HbA1c < 7%; the safety outcome was hypoglycemia risk. We identified 14 RCTs comprising 5326 patients with untreated T2DM. Mean treatment duration was 28.1 weeks. Pooled results showed that compared to metformin monotherapy, combination therapy was associated with a reduction in HbA1c (mean difference: −0.48 %, −0.58 to − 0.38) and FPG (mean difference: −0.92 mmol/L, −1.14 to − 0.69), and more patients achieving HbA1c < 7% (odds ratio: 2.21, 1.87 to 2.60). Hypoglycemic events and people experiencing hypoglycemia were not different between 2 groups. Initial combination of metformin plus a low hypoglycemic risk antidiabetic drug may achieve better glycemic control, without a rise in hypoglycemia, in patients with untreated T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Today, environmental concerns push for new technologies to reduce our energy dependence on fossil fuels. The use of treated biogas in dual-fuel diesel engines is common as it has no major effects on engine performance and it only requires minor engine modifications, consisting mostly on premixing and injection timing advance. However, biogas itself cannot be directly used in engines because of degradation caused by acid attacks and sulfidation, making sulfur compound filtration a necessity. In this case, biogas use is economically competitive for relatively big installations with electrical power above ≈100–200 kW. Simple, low-costs solutions are needed for small installations (below 100 kW). The objective of this paper is to assess the degradation of a 3.1 kW diesel engine in dual-fuel mode with preheated untreated biogas with phase separation. The modifications on the engine consist only in an exhaust/biogas heat exchanger with phase separation and lubricant replacement with a higher total base number. These changes are relatively costless compared to removing sulfur from the biogas. A test engine did function for 550 h with preheated untreated biogas containing 2000 ppmv of H2S. The load was maintained at 60% of maximum load with 50% of diesel replacement with biogas. Degradation was monitored by visual inspection, weight and size measurements of engine parts, in-cylinder pressure measurements, and oil analysis. Dismantling of the engine at the end of the experiment showed almost negligible signs of degradation. For comparison purposes, a similar test was conducted on the engine with the same operating conditions but without biogas preheating or phase separation. The degradation observed was noticeably more important in that experiment as the oil total base number decreased faster and cylinder head gasket wear was more important. Biogas preheating with phase separation seems a promising low-cost alternative for biogas use in small farms as it limits acid attacks and sulfidation in engines. [Copyright &y& Elsevier]

Abstract: Background: Combination highly active antiretroviral therapy (HAART) has significantly decreased HIV-1 related morbidity and mortality globally transforming HIV into a controllable condition. HAART has a number of limitations though, including limited access in resource constrained countries, which have driven the search for simpler, affordable HIV-1 treatment modalities. Therapeutic HIV-1 vaccines aim to provide immunological support to slow disease progression and decrease transmission. We evaluated the safety, immunogenicity and clinical effect of a novel recombinant plasmid DNA therapeutic HIV-1 vaccine, GTU®-multi-HIVB, containing 6 different genes derived from an HIV-1 subtype B isolate. Methods: 63 untreated, healthy, HIV-1 infected, adults between 18 and 40 years were enrolled in a single-blinded, placebo-controlled Phase II trial in South Africa. Subjects were HIV-1 subtype C infected, had never received antiretrovirals, with CD4≥350cells/mm3 and pHIV-RNA≥50copies/mL at screening. Subjects were allocated to vaccine or placebo groups in a 2:1 ratio either administered intradermally (ID) (0.5mg/dose) or intramuscularly (IM) (1mg/dose) at 0, 4 and 12 weeks boosted at 76 and 80 weeks with 1mg/dose (ID) and 2mg/dose (IM), respectively. Safety was assessed by adverse event monitoring and immunogenicity by HIV-1-specific CD4+ and CD8+ T-cells using intracellular cytokine staining (ICS), pHIV-RNA and CD4 counts. Results: Vaccine was safe and well tolerated with no vaccine related serious adverse events. Significant declines in logpHIV-RNA (p =0.012) and increases in CD4+ T cell counts (p =0.066) were observed in the vaccine group compared to placebo, more pronounced after IM administration and in some HLA haplotypes (B*5703) maintained for 17 months after the final immunisation. Conclusions: The GTU®-multi-HIVB plasmid recombinant DNA therapeutic HIV-1 vaccine is safe, well tolerated and favourably affects pHIV-RNA and CD4 counts in untreated HIV-1infected individuals after IM administration in subjects with HLA B*57, B*8101 and B*5801haplotypes. [Copyright &y& Elsevier]

Abstract: Background: Imatinib is an effective treatment for patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP), but resistance to imatinib can occur. Second-generation BCR-ABL inhibitors have shorter onset times and higher rates of complete cytogenetic response (CCyR) than imatinib. Dasatinib has a half-maximal inhibitory concentration 325 times lower than imatinib for BCR-ABL substrate phosphorylation in vitro and is less susceptible to most known molecular mechanisms of BCR-ABL imatinib resistance. Objectives: This study summarized published data on the use of dasatinib in CML-CP, reviewed the importance of early response to therapy, and discussed additional therapies for patients with newly diagnosed disease. Methods: PubMed was searched through June 2011 for English-language publications with the following search terms: imatinib, dasatinib, nilotinib, chronic myeloid/myelogenous leukemia or CML, and clinical trial. To identify follow-up data from published trials and data on trials in progress and products in development, similar searches were conducted for abstract and clinical trial databases. Relevant articles and abstracts were identified as those reporting results of Phase II and III clinical trials, predictors of treatment response, and treatment guidelines. No prespecified inclusion or exclusion criteria were used. Results: Dasatinib was effective in patients resistant to imatinib and more effective than high-dose imatinib in patients with newly diagnosed CML who were resistant to standard dose imatinib. Compared with imatinib, dasatinib induced superior response rates and patient outcomes earlier in the disease. In a Phase III trial in patients with newly diagnosed CML-CP, dasatinib 100 mg once daily induced significantly higher and faster rates of confirmed CCyR and major molecular response by 12 months versus imatinib and was generally well tolerated. Early achievement of CCyR was associated with better long-term progression-free survival. Dasatinib was approved by the U.S. Food and Drug Administration and the European Medicines Agency for initial treatment of CML-CP. Conclusions: Dasatinib was an effective treatment with the potential to improve long-term outcomes for patients with newly diagnosed CML-CP. [Copyright &y& Elsevier]

Summary: Nasopharyngeal carcinoma (NPC) is a non-lymphomatous carcinoma that develops in the epithelial lining of the nasopharynx. The knowledge of natural course of tumor progression has been based on anatomical model without clinical correlation. This study is the first to describe and analyze the natural progression of NPC based on clinical information and calculate the tumor growth rate of NPC. Fifteen NPC patients who refused treatment after initial work-up and then subsequent re-presentation at a later time were recruited during the period from January 2003 to August 2009. Clinical data were analyzed and CT scans were used to calculate the tumor volumes. The time interval between the first planning CT image and the subsequent planning CT image was used to calculate the rate of tumor growth in this group of patients. The tumor volume doubling time can be calculated by using the formula , where t is the time interval between measurements and V 2 and V 1 are the tumor volumes at the end and beginning of the time interval, respectively. Cranial nerves palsies such as diplopia and systemic upset were the most common reason for re-presentation and the consent for treatment. The median growth rate was 1.63mm3 per day and the median tumor doubling time was 279days. This study is the first report in the literature looking at the natural progression of nasopharyngeal carcinoma (NPC) based on clinical information. The current study showed that NPC has a propensity to grow superiorly to involve the skull base rather than laterally or anteriorly. Although the tumor growth rate was very variable, the median natural NPC growth rate was 1.63mm3/day. [Copyright &y& Elsevier]

Abstract: Introduction: Antipsychotic medication and lifestyle factors are implicated in the high rates of obesity and metabolic syndrome in schizophrenia. While the two Consensus Statements made in 2004 concluded they were unclear whether psychiatric disorders per se accounted for increased prevalence of metabolic disorders several later studies have presented the case for an association between schizophrenia and metabolic disorders, especially impaired glucose metabolism and Type 2 diabetes mellitus, independent of antipsychotic drug treatment. Methods: This is a comparative study of 51 patients with chronic schizophrenia who never received antipsychotic drug treatment and 51 healthy controls. Physical and laboratory assessments were made to measure body-mass index and diagnose metabolic syndrome using the International Diabetes Federation (2006) criteria. Results: The study observed a significantly lower mean body-mass index in patients (19.4) than controls (22.7) and very low and comparable rates of metabolic syndrome (3.9% in patients, 7.8% in controls). Discussion: Economic affordability and lifestyles modified by living conditions were discussed as factors underlying the high rates of underweight in the patient population and low rates of metabolic disorders in all the study subjects. The study concluded that schizophrenia in the absence of antipsychotic drug treatment is not a factor contributing to high prevalence of metabolic abnormalities. Lifestyle factors and the social and economic circumstances that drive them should be considered for better understanding and management of excess weight gain and metabolic abnormalities in people with schizophrenia. [Copyright &y& Elsevier]

Abstract: Objectives: The aim of the study was to prospectively examine all patients with a diagnosis of RLS consulting a sleep disorders clinic and to assess RLS severity and augmentation and their associations, including ferritin levels. Methods: Patients were stratified into patients with RLS as ancillary diagnosis, RLS sufferers without current augmentation and RLS sufferers with current augmentation. Work-up included RLS severity scales and blood biochemical variables including indices of iron metabolism. Results: In an 18-month period, 302 patients with RLS (183 women, 119 men; mean age, 59.1±13.7 years) were recruited. RLS was considered idiopathic in 291 patients (96.4%). Most patients (240, 79.5%) were RLS sufferers, whereas the remaining 62 (20.5%) had RLS as ancillary diagnosis. Nineteen out of 162 patients treated with dopaminergic agents (11.7%) had current augmentation. Almost one-third of all patients (31.1%) had ferritin levels <50μg/l. Patients with an ancillary diagnosis of RLS had higher ferritin levels than RLS sufferers without current augmentation. The lowest ferritin levels were present in RLS sufferers with current augmentation 132.8±98.0μg/l vs. 100.6±84.5μg/l vs. 55.8±43.6μg/l; p =0.002). Patients with augmentation did not differ from non-augmented patients regarding age, gender, RLS etiology, presence of previous augmentation, or any other documented comorbidity (p >0.05). Conclusion: The severity spectrum of RLS in this clinical cohort ranged from the ancillary diagnosis of RLS to augmented RLS. There was an inverse correlation between RLS severity and ferritin levels. Patients with current augmentation had the lowest ferritin levels. Our data further strengthen a putative role of low iron stores as a potential aggravator of idiopathic RLS. Moreover, low ferritin might represent a potential biomarker of RLS augmentation under dopaminergic therapy. [Copyright &y& Elsevier]

Thalidomide – either alone or in combination with dexamethasone or chemotherapy – has shown significant activity in relapsed/refractory disease. When used in the induction regimens in untreated patients, it significantly increases the response rates as well progression-free survival. Moreover, thalidomide as a maintenance therapy has become a very attractive option. However, the toxicity profile of the drug, mainly neurotoxicity and thrombotic events, mandate careful monitoring of patients treated with thalidomide, whether as the first line, in the relapsed setting, or as maintenance. In this chapter we will review the pharmacology, mechanisms of action, and toxicity of the drug, and will focus on available data from clinical experience and randomized trials of thalidomide in the different settings of multiple myeloma: refractory/relapsed disease, upfront treatment in patients who are eligible for high-dose therapy as well as those who are not, and finally the use of thalidomide as a maintenance treatment. [Copyright &y& Elsevier]

Summary: Background: Several studies have reported reduced heart rate variability (HRV) in patients with chronic epilepsy under treatment with antiepileptic drugs. This impairment in cardiac autonomic control might be of relevance in relation to the risk of sudden unexpected death in patients with chronic refractory epilepsy. Little information is, however, available on HRV in untreated patients with newly diagnosed epilepsy. Methods: We used spectral analysis to assess HRV based on 24h ambulatory EKG recordings in 22 consecutive untreated patients with epilepsy (15 with localization-related, 4 with generalized idiopathic and 3 with undetermined epilepsy). The HRV in these patients was compared with 22 age and sex matched healthy controls. Results: When analysing the full 24h recordings, there were no significant difference between the patients and the controls in any of the analyzed measures of HRV: standard deviation of RR-intervals (P =0.191), total power (P =0.170), very low frequency power (P =0.329), low frequency power (LF) (P =0.161), high frequency power (HF) (P =0.186) and the LF/HF ratio (P =0.472). The results were very similar for daytime and nighttime recordings. Conclusion: Our results suggest that there is no major effect of epilepsy as such on HRV in patients with untreated epilepsy. It should be emphasized that this study assessed newly diagnosed patients and that the results may not be applicable to patients with chronic epilepsy. [Copyright &y& Elsevier]

Objective: This study was undertaken to assess the natural course of endometrial endometrioid carcinoma by identifying untreated patients and those with a prolonged (> 6 months) treatment delay. Study design: A chart review of 252 patients with histologically confirmed endometrial endometrioid carcinoma was conducted and clinical data of untreated patients and those with a prolonged treatment delay were abstracted. Results: Seven patients (3 untreated and 4 with prolonged treatment delay) were identified. Five had clinical stage 1 and 5 had well-differentiated tumors. The survival of the untreated patients ranged from 5 to 59 months. Of the patients with prolonged treatment delay, 2 died more than 5 years after diagnosis and 2 are alive more than 5 years after diagnosis. Conclusion: The lengthy survival of our patients seems to indicate that the natural progression course, even in untreated patients, may be very slow in endometrial endometrioid carcinoma with favorable prognostic factors. [ABSTRACT FROM AUTHOR]

Creatine, which is well known as an important substance for muscular activity, is synthesized from amino acids such as glycine, arginine and ornithine in liver and kidney. It then accumulates in skeletal muscle as creatine phosphoric acid. The aim of this study was to understand the dehydration behavior of untreated and pulverized creatine monohydrate at various temperatures. The removal of crystal water was investigated by using differential scanning calorimetry (DSC), X-ray powder diffraction and scanning electron microscopy (SEM). The X-ray diffraction pattern of untreated and pulverized creatine monohydrate agreed with reported data for creatine monohydrate. However, the diffraction peaks of the (1 0 0), (2 0 0) and (3 0 0) planes of pulverized creatine monohydrate were much stronger than those of untreated creatine monohydrate. On the other hand, the diffraction peaks of the (0 1 2) and (0 1 3) planes of untreated creatine monohydrate were much stronger than those of pulverized creatine monohydrate. The dehydration of untreated and pulverized creatine monohydrate was investigated at various storage temperatures, and the results indicated that untreated and pulverized creatine monohydrate were transformed into the anhydrate at more than 30 °C. After dehydration, the particles of untreated and pulverized creatine anhydrate had many cracks. The dehydration kinetics of untreated and pulverized creatine monohydrate were analyzed by the Hancock–Sharp equation on the basis of the isothermal DSC data. The dehydrations of untreated and pulverized creatine monohydrate both followed a zero-order mechanism (Polany–Winger equation). However, the transition rate constant, calculated from the slope of the straight line, was about 2.2–7.7 times higher for pulverized creatine monohydrate than for untreated creatine monohydrate. The Arrhenius plots (natural logarithm of the dehydration rate constant versus the reciprocal of absolute temperature) of the isothermal DSC data for untreated and pulverized creatine monohydrate were linear. The activation energies of dehydration in the 40–60 °C range for untreated and pulverized creatine monohydrate were 15.02 and 10.1 kJ/mol, respectively. Dehydration of untreated creatine monohydrate had a pronounced effect on the particle size of the powder. Compared with pulverized creatine monohydrate, the particle size of untreated creatine monohydrate was significantly decreased by dehydration. [Copyright &y& Elsevier]

The method of quantitative analysis for untreated hair samples, which we developed three years ago, has proved to be quite useful for investigating environments contaminated by certain toxic elements. In the present work, the experimental conditions are improved. Loss of certain elements owing to irradiation damage, which has remained as one of the experimental uncertainties, was examined. It was found that the concentration of sulfur decreases gradually throughout the irradiation, while for the other elements, including arsenic and mercury, no changes occur under our measuring conditions. Furthermore, the degree of alteration of elemental concentration depending on the position along the hair was investigated. As a result, concentrations of some elements at different positions on a 14-cm-length hair, which was taken from a small-scale miner in the Philippines, showed some dependence on the distance from the root reflecting her history as a miner, while mercury does not show large deviation from a main trend. It was also found that concentration of mercury in hairs taken from different parts of a body does not show large difference. These results demonstrate that mercury and arsenic concentration in hairs, obtained by the present method, become a good index for an estimation of human exposure to these toxic elements. Changes of concentration of some elements depending on the way of cleaning before irradiation are studied in detail and the optimum way of washing is established. [Copyright &y& Elsevier]

• No comprehensive and objective classification system available for the evaluation of deformities in walking clubfoot with limited resources in healthcare setup. • Study was planned for generating an appropriate classification of severity of walking children with persistent clubfoot deformity to plan the effective management. • Anthropometry, Foot Imprinting, Radiography and Ultrasonography parameters were studied. • A new objective and practical classification system is developed using the parameters from above mentioned modalities. Clubfoot is one of the most common congenital deformities that cause mobility impairment. In developing countries, however, due to lack of appropriate medical care, treatment is either not initiated or incompletely performed. Due to lack of consensus for evaluation of deformities in such patients, there is no standardized treatment protocol yet developed. So, a new evaluation system is devised to assess the deformity in untreated or previously managed conservatively clubfoot of walking children. It was a prospective, observational study, conducted from December 2017 to July 2019. Patients from age 1–5 years, with unilateral deformity and previously managed conservatively were included. Patients having atypical clubfoot, syndromic clubfoot, or previously surgically intervened were excluded. Pre-treatment severity was graded with Diméglio score. Anthropometric, Foot Imprinting, Radiographic angles, and Ultrasonographic measurements were taken. Parameters taken were assessed and correlated with gradings of Diméglio score. 37 patients with mean age of 2.14 ± 0.87 years were included. Diméglio score was 11.57 ± 2.15 with 28 patients in 'severe' category. Talocalcaneal index and Tibiocalcaneal angle were correlating with the equinus whereas Bean shape ratio and Talocalcaneal index were correlating with varus deformity. Derotation of calcaneoforefoot block gradings correlating with Foot bimalleolar angle, Talo-first metatarsal angle, and MMN (medial malleolus to navicular distance) Ratio. FBM (Foot Bimalleolar) Angle, Talo-first metatarsal angle, MMN Ratio, and Medial soft tissue thickness were correlating with forefoot adduction. Following the correlation, a new classification system was devised to assess the severity of deformity at presentation. It is essential to develop an objective methodology to evaluate the severity of the clubfoot; whether the foot is responding to manipulation and casting; to detect the early signs of recurrences and predict the outcomes. The evaluation system should take into consideration the complex characteristics of the deformity and its three-dimensional aspects. [ABSTRACT FROM AUTHOR]

• We present an observational study on long-term prognosis of RMS patients never DMT. • 1186 RMS patients with a mean of 17.4 years follow-up were included. • 3 groups: DMT, untreated by shared (USD) or patient-autonomous decision (UAD). • USD was associated with lower risk for SPMS conversion compared to DMT. • UAD was associated with increased SPMS conversion risk compared to DMT. : The frequency and long-term prognosis of relapsing multiple sclerosis (RMS) never receiving disease-modifying treatment (DMT) is unclear. : We included 1186 RMS patients with a mean of 17.4 years follow-up and divided them into patients treated with any DMT (DMT) and patients untreated by shared (USD) or patient-autonomous decision (UAD). : The USD group displayed features, which significantly differed from the two other groups: higher age at onset, mainly sensory onset symptoms, complete remission of onset symptoms, less T2 and contrast-enhancing T1 lesions on initial brain MRI. In a multivariate cox regression, USD was associated with lower risk for secondary progression (SPMS) conversion (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.55–0.97, p = 0.011) compared to DMT, while UAD was associated with an increased SPMS conversion risk only in the "McDonald era" (HR 1.19, CI 1.02–1.58, p = 0.028). : Apart from the doubtless substantial improvement of the overall prognosis of RMS by DMT, it seems likely that not every patient necessarily needs immediate or even "hard and early" treatment. A "watchful waiting" approach with continuous clinical evaluation might be instead a viable option in RMS patients with favorable prognostic features at onset. [ABSTRACT FROM AUTHOR]