How unknown is metastatic carcinoma to cervical lymph nodes from an unknown primary?

BACKGROUND: The term metastatic carcinoma to cervical lymph nodes from an unknown primary includes a small group of tumors that present themselves with metastases to the cervical nodes, and in which diagnostic methods do not reveal the primary source of these metastases. Histologically, in most cases, these are metastases of squamous cell carcinoma. Carcinomas of unknown primary metastatic to cervical nodes account for < 5% of carcinomas of unknown primary and < 5% of head and neck cancers. The optimal treatment has not yet been defined. In the absence of distant metastases, the intention of treatment is curative. Patients are treated mostly with combined approaches including surgery, radiotherapy, or concomitant chemoradiotherapy. Radiotherapy is part of the treatment algorithm in most of the referenced works and includes irradiation of the mucosal sites of the pharyngeal axis as a potential localization of the primary tumor and unilateral or, more often, bilateral irradiation of the neck. Due to the higher risk of late toxicities observed, individualization of irradiated volumes based on the extent of the disease or other clinical parameters is a rational way to reduce these risks.  Purpose: The presented work discusses the treatment options for patients with metastatic carcinoma to cervical lymph nodes from an unknown primary. Furthermore, the work reports on the high effectiveness of curative radiotherapy in this group of tumors.

EXERCISE AND MICRORNA.

Physical activity stimulates numerous structural, metabolic, and morphological adaptations. These adaptations are vital for maintaining human health throughout life. Developments in molecular biology, biochemistry, and bioinformatics, along with exercise physiology have identified many signaling pathways, and transcriptional and translational processes responsible for exercise-related adaptations. The molecular mechanisms underlying the beneficial effects of exercise are not fully understood. Recently, the focus has been on microRNAs (miRNAs). They are small noncoding RNA molecules that negatively modulate gene expression and are involved in fundamental biological processes. This review describes miRNAs whose activities change in the heart, skeletal muscle, and circulation due to exercise. In addition, miRNAs with altered activity may be parameters adaptation to exercise, preventing injuries, and monitoring health status.

Chemoradiotherapy in the treatment of cervical cancer - a single institution retrospective review.

BACKGROUND: The aim of this study is a retrospective analysis of treatment outcomes and toxicity in a group of patients with cervical cancer who underwent (chemo) radiotherapy at the Institute of Radiation Oncology in Bulovka University Hospital in Prague in the period 2014-2017. PATIENTS AND METHODS: During this period, 141 patients were treated, 105 (74.5%) of them underwent combined (chemo) radiotherapy with radical intent and palliative radiotherapy was performed in 36 (25.5%) cases. According to the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification, the most numerous stages were IIB in 39 (27.7%) and IIIB in 64 (45.4%) cases; according to FIGO 2018, a significant number of newly established stages is evident: IIIC1 in 55 (39.0%) patients and IIIC2 in 22 (15.6%) cases. RESULTS: The median progression-free survival (PFS) and overall survival (OS) reached 31.3, resp. 40.1 months in the whole group. In the subgroup of patients treated with radical intent, the median PFS was 44.0 months and OS 48.8 months; in the palliative subgroup, the median PFS was 9.4 months and OS 14.8 months. In a radically treated subgroup, 7 (6.7%) patients had gastrointestinal or genitourinary manifestations of G3-4 toxicity, and overall acute toxicity (including skin and haematological reactions) of G3-4 occurred in 18 (17.1%) patients. Late toxicity of G3-4 was reported in 13 (12.4%) cases. Patients who underwent complete brachytherapy (BRT) showed significantly better survival compared to patients with a lower number of BRT fractions. The prognostic potential of PS (performance status) and anemia was confirmed; significantly longer overall survival was observed in patients in good general condition or in those without anemia. CONCLUSION: Our results confirmed the key role of BRT for the delivery of the curative dose to the target volume. The prognostic role of PS and anemia is evident. The side effects were in acceptable limits but we expect improvements because of the use of modern radiotherapy technologies.

Molecular and IHC analysis of head and neck carcinomas associated with HPV infection.

Head and neck squamous cell carcinomas (HNSCC) are a highly heterogenous disease which can be induced by two main carcinogens - tobacco and/or alcohol, or by HR HPV infection. This work examined 60 paraffin-embedded biopsies of head and neck carcinomas after histological verification. HPV infection, including its specific types in various HNSCC areas, was studied using multiplex qPCR. Expression levels of p16INK4A and p53 were detected by subsequent IHC analysis as being potential diagnostic markers. Based on the assumption that patients with HNSCC could benefit from anti-EGFR therapy (cetuximab), but the predictors are not yet defined, analyses of point mutations of ras genes (Kras, Nras) were carried out using multiplex qPCR and sequence analysis of the Braf gene. All statistical data were processed by Chí-x2 test.HPV infection was detected in 23.34 % of cases with HNSCC, of which 100 % were HPV 16, which is the most frequently infection found in the oropharyngeal region. Using IHC analysis, a positive expression of P16INK4A was detected in 100 % of HPV-positive HNSCC while this expression was discovered to be highly correlated with HPV infection. Furthermore, a correlation between p53 and HPV-negative HNSCC was proved. The mutation incidence was the highest in the Kras gene (codon 12 and codon 146), Nras (codon 12) and Braf. A correlation between tumor location in the oropharyngeal region and Kras mutations was proved. The HPV infection correlated with Kras mutations in case of codon 146 but on the grounds of low amount of output data, these figures could be irrelevant. In one case, c.1808 G>A, protein 603 Arg>Gln mutation was found in the Braf gene but its correlation with head and neck carcinomas has not been described yet (Tab. 2, Fig. 2, Ref. 24). Keywords: head and neck carcinomas, biopsy, HPV types, PCR, p16INK4A, p53, molecular predictors, Kras, Nras, Braf.

Untangling Neolithic and Bronze Age mitochondrial lineages in South Asia.

Two key moments shaped the extant South Asian gene pool within the last 10 thousand years (ka): the Neolithic period, with the advent of agriculture and the rise of the Harappan/Indus Valley Civilisation; and Late Bronze Age events that witnessed the abrupt fall of the Harappan Civilisation and the arrival of Indo-European speakers. This study focuses on the phylogeographic patterns of mitochondrial haplogroups H2 and H13 in the Indian Subcontinent and incorporates evidence from recently released ancient genomes from Central and South Asia. It found signals of Neolithic arrivals from Iran and later movements in the Bronze Age from Central Asia that derived ultimately from the Steppe. This study shows how a detailed mtDNA phylogeographic approach, combining both modern and ancient variation, can provide evidence of population movements, even in a scenario of strong male bias such as in the case of the Bronze Age Steppe dispersals.

Metal sorption by biochars: A trade-off between phosphate and carbonate concentration as governed by pyrolysis conditions.

Three feedstocks, pine wood, grass and cow manure, were pyrolyzed under various conditions and tested on their ability to sorb metals in aquatic systems. The feedstocks were pyrolyzed at 2 different temperatures (350 °C and 550 °C) and 2 different residence times (10 and 60 min) and resulting biochars were assessed on their capability to immobilize Pb, Cu, Cd and Zn. Manure-based chars, and to a lesser extent grass-based chars, featured high concentrations of phosphates and carbonates. These anions play an important role in metal sorption because they form insoluble complexes with the metals. Washing reduced the concentration of these anions, leading to a reduced sorption of metals by the biochar. The carbonate concentration on the biochars' surface increased at higher reactor temperature and longer residence times. The opposite trend was observed for the phosphate concentration and the cation exchange capacity. Accordingly, the optimal temperature-residence time combination for sorption was a trade-off between these properties. Biochar produced from cow manure and pyrolyzed at 550 °C for 10 min showed the best sorption for all metals considered.

Effects of thymoquinone on liver miRNAs and oxidative stress in Ehrlich acid mouse solid tumor model.

We investigated the effects of thymoquinone (TQ) on the expression of liver microRNAs (miRNAs), liver histopathology and oxidative stress in Ehrlich acid solid tumor model induced mice. We used 24 male BALB/c mice divided randomly into three groups. Control (C) group mice were injected intraperitoneally (i.p.) with 0.5 ml saline for four weeks. Tumor (T) group mice were injected i.p. with 0.5 ml saline for four weeks, then Ehrlich acid tumor cells were injected subcutaneously into the neck to induce solid tumor formation. TQ (T + Tq) group mice injected i.p. with 10 mg/kg TQ for four weeks, then Ehrlich acid tumor cells were injected subcutaneously into the neck of the mice in this group to induce solid tumor formation. At the end of the study, liver from all groups were removed for histopathological and miRNAs analysis, and oxidative stress measurement. We found that the expression of miR-206b-3p was up-regulated and the oxidative stress and necrosis increased in the liver tissue of mice with Ehrlich acid solid tumor. TQ application decreased the oxidative stress, prevented necrosis, increased regeneration and down-regulated the expression of miR-206b-3p in the liver tissue.

Seasonal variation of human semen parameters: A retrospective study in Italy.

INTRODUCTION: Human infertility is a common condition secondary to many primary or secondary causes. As for these latter, different seasonal and climatic patterns have been hypothesized to play a role. The aim of this study was to assess the presence of a possible seasonal pattern in the functional parameters of semen samples maintained in a large tertiary center database. MATERIALS AND METHODS: The reports of spermograms of 5188 consecutive subjects, collected at the Center for Reproductive Incapacity of the University Hospital of Parma during a 11-year period (2003-2014), were retrospectively analyzed. The reports included sperm motility, volume, and number, as well as pH, swelling and eosin tests. Data of different parameters were analyzed by season of sample collection. The ANOVA test was used for the evaluation of continuous variables, after Log transformation in case of a non-normal distribution, while χ(2) test was used for categorical variables. Moreover, logistic regression analysis was performed, to identify factors independently associated with normal sperm motility. RESULTS: Compared with the other seasons of the year, a higher sperm motility was found during the summer. Moreover, the prevalence of samples with a normal sperm pH (7.2-8) was higher during the spring, whilst the volume of sperm was higher in winter. Logistic regression analysis showed that normal sperm motility (>40%) was independently associated with spring (1.227; 95% CI 1.077-1.507, p = 0.005), summer (2.031; 95% CI 1.689-2.442, p < 0.001), swelling test (1.953; 95% CI 1.670-2.284, p < 0.001), eosin test (2.804; 95% CI 2.477-3.174, p < 0.001), pH (0.507; 95% CI 0.346-0.743, p < 0.001), LOG-number (2.949; 95% CI 2.470-3.522, p < 0.001) and LOG-volume (2.216; 95% CI 1.696-2.894, p < 0.001) of semen. CONCLUSION: This study suggests the existence of a positive relationship between some semen parameters and seasons.

Uric acid: friend or foe? Uric acid and cognitive function "Gout kills more wise men than simple".

OBJECTIVE: The association between hyperuricemia and cardiovascular risk is widely known, and hyperuricemia is associated with many pathological conditions due to its effect on the endothelial function and metabolic homeostasis. The aim of this study was to verify whether the available literature may support the hypothesis that uric acid has a protective and stimulating effect on the cerebral cortex. MATERIALS AND METHODS: We reviewed the actual knowledge of the positive effects of uric acid in terms of antioxidant action, neuroprotection, cognitive function, and intellectual performance. CONCLUSIONS: Uric acid has a stimulating effect on the cerebral cortex, and this could have allowed humans, compared with other animals, to develop higher brain mass volume, better intellectual performances, and maybe evolutionary supremacy. On the other, a growing body of evidence is accumulating on the independent association between uric acid and cardiovascular risk. A careful interpretation of uric acid levels is appropriate and necessary in different kinds of patients, both at risk of cardiovascular or neurodegenerative diseases, due to its contrasting significance.

Mitochondrial DNA lineages of Italian Giara and Sarcidano horses.

Giara and Sarcidano are 2 of the 15 extant native Italian horse breeds with limited dispersal capability that originated from a larger number of individuals. The 2 breeds live in two distinct isolated locations on the island of Sardinia. To determine the genetic structure and evolutionary history of these 2 Sardinian breeds, the first hypervariable segment of the mitochondrial DNA (mtDNA) was sequenced and analyzed in 40 Giara and Sarcidano horses and compared with publicly available mtDNA data from 43 Old World breeds. Four different analyses, including genetic distance, analysis of molecular variance, haplotype sharing, and clustering methods, were used to study the genetic relationships between the Sardinian and other horse breeds. The analyses yielded similar results, and the FST values indicated that a high percentage of the total genetic variation was explained by between-breed differences. Consistent with their distinct phenotypes and geographic isolation, the two Sardinian breeds were shown to consist of 2 distinct gene pools that had no gene flow between them. Giara horses were clearly separated from the other breeds examined and showed traces of ancient separation from horses of other breeds that share the same mitochondrial lineage. On the other hand, the data from the Sarcidano horses fit well with variation among breeds from the Iberian Peninsula and North-West Europe: genetic relationships among Sarcidano and the other breeds are consistent with the documented history of this breed.

Prescription of oral antidiabetic drugs in K/DIGO chronic kidney disease stage 3 and 4: a single centre report.

AIM: Evaluation of chronic kidney disease (CKD) is essential in order to prescribe properly oral antidiabetic drugs (OADs). The aim of our study was to report hypoglycemic drugs prescription to CKD in a cohort of type 2 diabetes mellitus (DM) outpatients. METHODS: This survey included 1686 outpatients with type 2 DM treated with OADs who were not taking insulin evaluated by a team of diabetologists. Glomerular filtration rate (GFR) was calculated by the CKD-EPI formula and subjects were classified in the K/DIGO stages. Main clinical parameters were also evaluated. RESULTS: Patients were aged 68±10 years, 57.1% were males, Body Mass Index was 30±5 kg/m2, glycated hemoglobin 8±1%, systolic and diastolic blood pressure values were 138±15/80±9 mmHg. Serum creatinine was 1.03±0.35 mg/dL and GFR 71±21 mL/min/1.73 m2. In 504 patients (30%) GFR was lower than 60 mL/min/1.73 m2. The different treatment groups had different GFR and hypoglycaemic drugs were prescribed differently in the different K/DIGO stages. The majority of subjects in stage 3A and 3B were treated with repaglinide, however a significant percentage of them were treated with metformin and sulfonylureas. Nearly half of subjects with CKD stage 4 were treated with metformin and sulfonylureas. CONCLUSION: In this report we found that nearly one third of patients with type DM 2 had CKD and in a significant percentage of them OADs were prescribed even if they were in K/DIGO CKD stage 3 and 4.

The estimation of glomerular filtration rate in type 2 diabetic patients may depend on the equation used.

BACKGROUND: The aim of this study was to compare the estimation of glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM) outpatients. PATIENTS AND METHODS: The study included 1686 subjects, aged 68±10 years. GFR was evaluated with five different equations: GFRMDRD186, GFRMDRD175, GFRCKD-EPI, GFRMAYO, GFRC-G. RESULTS: GFR was lower than 60 ml min-1 kg-1 in 456 patients (27%) by GFRMDRD186, in 531 (31.5%) by GFRMDRD175, in 504 (30%) by GFRCKD-EPI, in 433 (26%) by GFRC-G, and in 255 (15%) by GFRMAYO. The mean differences in measuring GFR with the different formulae ranged from 1.03±6.20 to -14.5±11.9 ml min-1 1.73 m2-1. CONCLUSIONS: The evaluation of GFR with different formulae in type 2 DM patients may identify different chronic kidney disease (CKD) stages. Physicians could take advantage by the knowledge of the formula used for evaluation of renal function, for a better interpretation of values and a more appropriate use in the everyday clinical practice.

Invasive procedure for intractable epistaxis in an old comorbid woman: a case report.

Epistaxis is a condition mainly self-limiting or easily treated conservatively, although in rare cases it could become life-threatening. We discuss the case of a 73 year comorbid old woman with severe and recurrent epistaxis treated with superselective catheterism and embolization of the internal maxillary artery. The possible underlying causes, including drug related issues, are discussed.

Coherent tunnelling across a quantum point contact in the quantum Hall regime.

The unique properties of quantum hall devices arise from the ideal one-dimensional edge states that form in a two-dimensional electron system at high magnetic field. Tunnelling between edge states across a quantum point contact (QPC) has already revealed rich physics, like fractionally charged excitations, or chiral Luttinger liquid. Thanks to scanning gate microscopy, we show that a single QPC can turn into an interferometer for specific potential landscapes. Spectroscopy, magnetic field and temperature dependences of electron transport reveal a quantitatively consistent interferometric behavior of the studied QPC. To explain this unexpected behavior, we put forward a new model which relies on the presence of a quantum Hall island at the centre of the constriction as well as on different tunnelling paths surrounding the island, thereby creating a new type of interferometer. This work sets the ground for new device concepts based on coherent tunnelling.

Definitive radiochemotherapy with weekly cisplatin in patients with head and neck cancer; single institution outcome analysis.

PURPOSE: The objective of this study was to evaluate the feasibility, toxicity and efficacy of definitive radiochemotherapy with weekly cisplatin in head and neck cancer in a single institutional setting. METHODS: Previously untreated patients with stage II-IV head and neck cancer were included. Radiotherapy consisted of 70 Gy/7 weeks/35 fractions. All patients received concurrent cisplatin 40 mg/m(2) weekly. RESULTS: Between 2/2002 and 8/2009, 148 consecutive patients (WHO ≤ 2, male to female ratio 6/1, median age 56 years) were treated. The mean follow-up was 40 months. Tumors of the oropharynx were the most frequent (46%) and stage IV predominated (80%). Eighty-nine percent of the patients had received the full radiation treatment as planned. Omission of weekly cisplatin occurred frequently, mainly because of hematological toxicity. Only 64% of the patients completed at least 5 cycles of chemotherapy. Grade 3/4 mucosal toxicity developed in 32% of the patients. The late toxicities were acceptable: 74% of the patients were able to eat solid food during the 1st post-treatment year, 4 patients were not able to swallow at all during the 1st post-treatment year, requiring thus permanent feeding tube. Five cases of osteoradionecrosis of the mandible were reported. Three-year overall survival, locoregional control, time to progression and disease free survival were 34, 60, 52 and 29%, respectively. CONCLUSION: Definitive radiochemotherapy with weekly cisplatin was toxic, with high rate of morbidity and mortality in this patient population. Five weekly cycles of 40 mg/m(2) cisplatin seem to be the dose limit for most patients. Three-year survival was significantly reduced despite the promising high initial response and locoregional control.

Left kidney: an unusual site of cocaine-related renal infarction. A case report.

Acute renal infarction is a well known, although relatively unfrequent, cause of flank pain resistant to administration of spasmolytic and nonsteroidal anti-inflammatory drugs. We present an original case of a 41-year-old man, complaining of acute severe left flank pain, resistant to common analgesic therapy, who was diagnosed of segmental renal infarction of a branch of left renal artery. Pathophysiology of renal damage in cocaine users is multifactorial, and it has been postulated that the right kidney was more prone to ischaemia. Left kidney represents an extremely unusual site of cocaine-related renal infarction.

Transport inefficiency in branched-out mesoscopic networks: an analog of the Braess paradox.

We present evidence for a counterintuitive behavior of semiconductor mesoscopic networks that is the analog of the Braess paradox encountered in classical networks. A numerical simulation of quantum transport in a two-branch mesoscopic network reveals that adding a third branch can paradoxically induce transport inefficiency that manifests itself in a sizable conductance drop of the network. A scanning-probe experiment using a biased tip to modulate the transmission of one branch in the network reveals the occurrence of this paradox by mapping the conductance variation as a function of the tip voltage and position.

Cocaine and acute vascular diseases.

Cocaine is one of the most widely used drugs of abuse. Chest pain is the most common side effect requiring emergency visits after cocaine use. Vasoconstriction and platelet activation are the main effects of cocaine in the vasculature. In this brief review, we consider the most important clinical effects of cocaine abuse on the heart, brain and kidney. Symptoms related to cocaine toxicity such as myocardial infarction, congestive heart failure, arrhythmias, aortic dissection, stroke, renal failure, are similar to the clinical picture of atherosclerotic vascular damage, even if the age of cocaine abusers is usually in the second and third decades. Clinicians (especially emergency department physicians) should consider substance abuse among the differential diagnosis of chest pain in young people.