Early social and ecological experience triggers divergent reproductive investment strategies in a cooperative breeder.
Unlike eusocial systems, which are characterized by reproductive division of labour, cooperative breeders were predicted not to exhibit any reproductive specialization early in life. Nevertheless, also cooperative breeders face a major life-history decision between dispersal and independent breeding vs staying as helper on the natal territory, which might affect their reproductive strategies. In the cooperatively-breeding cichlid Neolamprologus pulcher early-life social and predator experiences induce two behavioural types differing in later-life social and dispersal behaviour. We performed a long-term breeding experiment to test whether the two early-life behavioural types differ in their reproductive investment. We found that the early-dispersing type laid fewer and smaller eggs, and thus invested overall less in reproduction, compared to the philopatric type. Thus N. pulcher had specialised already shortly after birth for a dispersal and reproductive strategy, which is in sharp contrast to the proposition that reproductively totipotent cooperative breeders should avoid reproductive specialization before adulthood.


Papilledema secondary to metastatic prostate disease.
Prostate cancer increases in incidence with age, and is common in older men. If allowed to progress or detected late, prostate cancer readily metastasizes to bone and accounts for about 11 percent of all cancer deaths. Associated conditions with prostate metastatic disease are anemia, pathological bone fractures, and paraplegia. Occasionally, prostate cancer may metastasize to the skull or spinal cord and result in papilledema. Two cases presenting with papilledema secondary to metastatic prostate disease are discussed.


Proteomic analysis to improve adequacy of hemo- and peritoneal dialysis: Removal of small and high molecular weight proteins with high- and low-flux filters or a peritoneal membrane.
The reduction of morbidity and mortality in patients undergoing hemo- or peritoneal dialysis is strongly related to an efficient and selective clearance of uremic toxins. We used proteomics methods to analyze and further characterize the dialytic removal of still undefined middle and high molecular weigh proteins as a basis for further improvement of dialysis assessment. Dialysates from 26 hemodialysis patients treated with different types of low- (F6HPS®) and high-flux (FX80®, APS650®, FX60®) filters as well as peritoneal fluids from 10 continuous ambulatory peritoneal dialysis (CAPD) patients were analyzed by SELDI-TOF and 2-DE. The protein patterns showed selective differences in the proteins cleared depending on the dialysis method used and the filter membrane. While SELDI analyses of dialysates from the F6HPS revealed almost no protein clearance, high-flux filters and CAPD dialysates showed protein release of different molecular weight ranges. Furthermore, 2-DE and MS analysis identified 48 different proteins from the dialysate of high-flux filters and 21 from peritoneal dialysis fluids. In F6HPS dialysates, however, only few proteins could be identified.


Recurrent peripheral giant cell granuloma associated with cervical resorption.
A case of recurrent peripheral giant cell granuloma in a 38-year-old man is reported. The lesion was localized on the attached gingiva of the lower left second premolar (tooth #35). The surgical excision of the lesion revealed a superficial resorption of the cervical region of the involved tooth. The resorption was smoothed out, and there was no sign of recurrence or further resorption after 14 months. Root resorption, although extremely rare, may be associated with peripheral giant cell granuloma.


Biochemical basis of DDT-resistance in Aedes aegypti population from a dengue affected area in Shahjahanpur city.
Entomological studies conducted in Jalalnagar, Shahjahanpur city, Uttar Pradesh, India, during an outbreak of dengue in 1992, showed that Ae. aegypti mosquitoes were resistant to DDT and had some tolerance to malathion in the adults and the larvae. Biochemical analysis suggested that DDT resistance was related to elevated glutathione s-transferase and tolerance to malathion was due to a little increase in esterase activity. Crosses of DDT-resistant and susceptible strain suggested that resistance was codominant (metabolic type).


Impact of the IADPSG criteria for gestational diabetes, and of obesity, on pregnancy outcomes.
The adoption of the International Association of Diabetes Study Groups (IADPSG) criteria for gestational diabetes mellitus (GDM) in Australia has been controversial. Obesity in pregnancy is also a growing concern. To assess the impact of IADPSG criteria on the incidence of GDM and pregnancy outcomes, and to compare this to the effect of obesity, particularly among women who would not have GDM by the Australasian Diabetes in Pregnancy Society 1998 criteria (ADIPS1998). A retrospective observational cohort study linking results of 75 g glucose tolerance tests with demographic and pregnancy data was conducted. In our cohort of 6175 pregnancies, GDM was present in 926 (15%) women by the ADIPS1998 criteria; it increased to 1098 (17.8%) women by the IADPSG criteria. Among the 5248 pregnancies which did not meet the ADIPS1998 criteria and were not treated for GDM, women with IADPSG GDM had increased risk of gestational hypertension, pre-eclampsia, induction of labour (IOL), primary caesarean section (PCS) and large for gestational age (LGA) compared to women without GDM (all P < 0.05), whereas obese women had increased risk of gestational hypertension, pre-eclampsia, IOL, PCS, small for gestational age (SGA) and shoulder dystocia compared to women of normal weight (all P < 0.05). On multivariate analysis, IADPSG GDM was an independent risk factor only for IOL (P = 0.04) and LGA (<0.001). Obesity was an independent risk factor for gestational hypertension, pre-eclampsia, IOL, PCS, shoulder dystocia and SGA (all P < 0.001). Within our population, of women who are not currently treated for GDM, obesity is associated with greater pregnancy risk than GDM diagnosed by IADPSG criteria.


Medical ethics in ancient times.
Moral self-regulation is all the more important in ancient medicine since medical training and practice in the Greek-Roman world were not subjected to any legal or state regulations. Physicians on the one hand had to acquire scientific skills, through voluntary efforts, and on the other hand had to offer the image of a "friend-physician" with respect for the personality of the patient. This code of conduct would distinguish the professionally serious physician from the many quack-doctors who claimed to be healers. Conversely, the famous text of the so called "Hippocratic Oath" cannot be considered as a significant example of the prevailing positions in ancient medicine, because it draws inspiration from philosophical-religious concerns typical of the Pythagoric sect.


Tc-99m MIBI uptake in simultaneous thyroid and lung cancers.
The authors present a patient with simultaneous follicular thyroid and small-cell lung cancers, both of which showed Tc-99m MIBI uptake. CT scans showed two masses: one involving the right lower neck including the right supraclavicular area and the right superior mediastinum, and the other involving the peripheral portion of the right upper lobe of the lung. I-131 imaging showed increased uptake in the right neck mass only. Tc-99m MIBI imaging, which was performed for evaluation of chest pain, showed intense uptake in the neck mass (tumor to heart ratios in planar and tomographic images were 0.92 and 0.96, respectively), and less uptake in the lung mass (tumor to heart ratios in planar and tomographic images were 0.53 and 0.40, respectively). Biopsy of the right supraclavicular mass revealed a follicular carcinoma, and a bronchoscopic biopsy of the right upper lobe mass revealed a small cell carcinoma.


Postnatal development of serotonergic innervation, 5-HT1A receptor expression, and 5-HT responses in rat motoneurons.
We compared the electrophysiological responses to serotonin (5-HT) of neonatal and juvenile rat hypoglossal motoneurons (HMs) by using intracellular recording techniques in a brainstem slice preparation. In neonatal HMs (</=P8), 5-HT caused a substantial decrease in the amplitude of spike afterhyperpolarization (AHP) that was associated with an increase in the minimal repetitive firing frequency (Fmin). Previous work has shown that this effect of 5-HT was mediated by the 5-HT1A receptor and may be secondary to inhibition of N- and P/Q-type calcium channels. In contrast to results from neonates, we found that 5-HT did not inhibit the AHP in juvenile HMs (>/= P20). Application of a cocktail of calcium channel toxins (omega-Conotoxin-GVIA and omega-Agatoxin-IVA) to juvenile HMs substantially inhibited the AHP, indicating that calcium entry through N- and P/Q-type channels supports the AHP in juvenile HMs, as it does in neonates. In addition, intracellular injection of the long-lasting GTP analog GTPgammaS induced an agonist-independent increase in Fmin similar to that seen in neonates in the presence of 5-HT. Together, these results suggested that intracellular mechanisms downstream of the 5-HT1A receptor capable of inhibiting the AHP were intact in juvenile HMs. Therefore, we investigated the possibility that age-related changes in effects of 5-HT on the AHP resulted from altered expression of the 5-HT1A receptor. To this end, we performed ligand-binding autoradiography using [3H]8-OH-DPAT, a 5-HT1A agonist, and in situ hybridization using radiolabeled oligonucleotide probes specific for the 5-HT1A receptor. The two approaches gave remarkably similar results. The highest levels of 5-HT1A receptor expression were found in neonatal HMs, with maximal binding and hybridization at approximately postnatal day 7 (P7) and only low levels of receptor expression by P28. Finally, immunohistochemistry for 5-HT revealed that these developmental changes in 5-HT1A receptor expression occurred coincident with a postnatal increase in serotonergic innervation of the hypoglossal nucleus (nXII). Together, these findings indicate that developmental changes occur in the serotonergic innervation of nXII and in the expression of 5-HT1A receptors in HMs during the early postnatal period, resulting in markedly different effects of 5-HT on firing behavior in neonatal and juvenile HMs.


[Effects of all-trans retinoic acid on the macrophage function of prostatic stromal cells].
To investigate the effects of all-trans retinoic acid (ATRA) on prostatic stromal cells during wound repair after prostatectomy in vitro. Each of the M1 and M2 types of monocytic macrophage (THP-1) cells were divided into an experimental, a control and a non-activated group, the M1 macrophages of the former two groups activated by PMA and IFNγ, and the M2 macrophages by PMA and IL-4, respectively. The cells in the two experimental groups were treated with all-trans retinoic acid (ATRA) at 100 nmol/L, followed by detection of the expressions of IL-10, IL-12, IL-6, TNF-α and TGF-β in the supernatant by ELISA. The supernatant was co-cultured with primarily cultured prostatic stromal cells or vascular endothelial cells in different groups. The expressions of RARα, RARβ, RARγ, Arg1, Mmp9 and Soat1 in the macrophages were determined by PCR. The influence of the macrophages on the function of the stromal cells was analyzed by gel shrinkage test, scratch test and vascular endothelial cell tubular vascular formation test. The expression levels of Arg1 mRNA were reexamined under the action of RAR receptor subtype inhibitors. Compared with the control, the M2 macrophages treated with ATRA showed dramatically up-regulated expressions of IL-10 ([213.38 ± 2.02] vs [298.22 ± 1.70] pg/ml, P < 0.01) and TGF-β ([185.37 ± 1.33] vs [246.00 ± 2.14] pg/ml, P < 0.01). The ATRA-treated macrophage supernatant enhanced the contraction and migration of the prostatic stromal cells and tubular formation of the vascular endothelial cells. The mRNA levels of Arg1 and RARβ were significantly increased in the experimental group, and RARβ was further confirmed to be the key receptor subtype in this process. ATRA activates prostatic stromal cells and enhances their migration and angiogenesis by acting on macrophages via RARβ.


Estimation of trabecular bone parameters in children from multisequence MRI using texture-based regression.
This paper presents a statistical approach for the prediction of trabecular bone parameters from low-resolution multisequence magnetic resonance imaging (MRI) in children, thus addressing the limitations of high-resolution modalities such as HR-pQCT, including the significant exposure of young patients to radiation and the limited applicability of such modalities to peripheral bones in vivo. A statistical predictive model is constructed from a database of MRI and HR-pQCT datasets, to relate the low-resolution MRI appearance in the cancellous bone to the trabecular parameters extracted from the high-resolution images. The description of the MRI appearance is achieved between subjects by using a collection of feature descriptors, which describe the texture properties inside the cancellous bone, and which are invariant to the geometry and size of the trabecular areas. The predictive model is built by fitting to the training data a nonlinear partial least square regression between the input MRI features and the output trabecular parameters. Detailed validation based on a sample of 96 datasets shows correlations >0.7 between the trabecular parameters predicted from low-resolution multisequence MRI based on the proposed statistical model and the values extracted from high-resolution HRp-QCT. The obtained results indicate the promise of the proposed predictive technique for the estimation of trabecular parameters in children from multisequence MRI, thus reducing the need for high-resolution radiation-based scans for a fragile population that is under development and growth.


Tension-free thyroidectomy (medial thyroidectomy)-a prospective study: surgical technique and results of 259 operations.
Thyroid surgery is associated with a number of surgical complications including recurrent laryngeal nerve (RLN) injury and hypoparathyroidism. The existing methods share the same principle-the mobilization of the thyroid from the lateral side. The aim of this study was to evaluate the safety of a novel technique of thyroidectomy-tension-free thyroidectomy (TFT) based on the medial approach to the laryngeal nerves and parathyroid glands (PTGs). The study was conducted between August 2021 and July 2022 in Saint Petersburg State University Hospital. A total of 261 patients with thyroid diseases were enrolled in the study and operated on using the TFT technique. The operations with the use of TFT technique were completed in all but two cases which required the conversion to the standard lateral approach. Of 259 TFT cases unilateral laryngeal paresis was registered in 6 (2.3%) cases or in 1.7% of the number of RLNs at risk. In all but one case the vocal fold function recovered in less than 6 months of the follow-up. Among 87 patients who underwent total thyroidectomy transient postoperative hypoparathyroidism was found in 10 cases (11.5%), rate of persistent hypoparathyroidism was 0%. One case of postoperative bleeding was recorded (0.4%). The TFT technique demonstrated high safety and several advantages over the traditional method of performing operations on the thyroid gland.


The study of elbow injury in male adult kendo players.
[Purpose] Elbow injury in male adult kendo players was investigated and examined in order to obtain an indicator of prophylaxis of injury. [Subjects and Methods] The subjects were 22 male adult kendo players aged 25 to 60 years old, and presence or absence of pain, range of motion, and muscle strength in the elbow joints were investigated. In addition, among athletes with limited range of motion (ROM) in the elbow joints, three athletes who had received an explanation and had provided informed consent underwent CT, and the images were examined. [Result] As a result, posterior pain and decreased range of extension motion in the right elbow were noted in 86% of the subjects, and the CT images showed free bone fragments and osteophytes in the olecranon. Also, characteristics were noted that extension muscle strength was stronger than flexion muscle strength in elbow muscle strength. [Conclusion] Based on these results, characteristic disorders in male adult kendo players include an impingement disorder in the posterior region of the right elbow.


Cryo-conditioned rocky coast systems: A case study from Wilczekodden, Svalbard.
This paper presents the results of an investigation into the processes controlling development of a cryo-conditioned rock coast system in Hornsund, Svalbard. A suite of nested geomorphological and geophysical methods have been applied to characterise the functioning of rock cliffs and shore platforms influenced by lithological control and geomorphic processes driven by polar coast environments. Electrical resistivity tomography (ERT) surveys have been used to investigate permafrost control on rock coast dynamics and reveal the strong interaction with marine processes in High Arctic coastal settings. Schmidt hammer rock tests, demonstrated strong spatial control on the degree of rock weathering (rock strength) along High Arctic rock coasts. Elevation controlled geomorphic zones are identified and linked to distinct processes and mechanisms, transitioning from peak hardness values at the ice foot through the wave and storm dominated scour zones to the lowest values on the cliff tops, where the effects of periglacial weathering dominate. Observations of rock surface change using a traversing micro-erosion meter (TMEM) indicate that significant changes in erosion rates occur at the junction between the shore platform and the cliff toe, where rock erosion is facilitated by frequent wetting and drying and operation of nivation and sea ice processes (formation and melting of snow patches and icefoot complexes). The results are synthesised to propose a new conceptual model of High Arctic rock coast systems, with the aim of contributing towards a unifying concept of cold region landscape evolution and providing direction for future research regarding the state of polar rock coasts.


[Biomass dynamics of tree branches of higher order. A model analysis].
The sectional model of biomass dynamics of freely growing tree brahcnes of all orders is presented. The model is an extension of the sectional tree biomass model proposed earlier. The branches model showed bell-shaped dynamics of a branches biomass and, accordingly, boundedness of branch orders number. The important element of the model of branches system is the inter-verticil green biomass. The model is parameterized on the basis of published data on lifespan of branches of different orders and age in which the biomass of skeletal branches of spruce, Picea abies (L.) Karst, reaches the maximum. When adding known peculiarities of spruce growth (such as the initial growth inhibiton and presence of the inter-verticil branches) to the model of biomass dynamics of regular branches system, good appproximation of all natural data by model values is obtained. The possible mechanism of inter-verticil branches appearance in response to improvement of a tree growth conditions, and also their function in a tree growth process, namely replacement of regular branches incapable of appropriate response, is described. Initiation of appearing and/or waking of the sleeping (adventive) buds which give rise to inter-verticil branches is probably caused by rise of pressure of photosynthates in a tree phloem what the published results of experiments on a decapitaion of branches of Wollemia nobilis (Araucariaceae) also testify.


Differences between healthy adults and patients with type 2 diabetes mellitus in reactivity of toe microcirculation by ultrasound combined with a warm bath test.
The aim of this study was to explore the feasibility and clinical value of ultrasound combined with a warm bath test in assessing the differences in reactivity of toe microcirculation between healthy adults and patients with type 2 diabetes mellitus (T2DM).A total of 56 T2DM patients were recruited as case group, whereas 50 healthy volunteers were enrolled as control group.Fasting blood glucose, glycated hemoglobin, total cholesterol, triglyceride, low-density lipoprotein cholesterol in T2DM group were significantly higher than in control group. Under stationary condition, peak systolic velocity (PSV), end-diastolic velocity (EDV), and mean velocity (MV) were lower, but pulsatility index (PI) and resistance index (RI) were higher in patients with T2DM than in controls both in dorsalis pedis artery (DPA) and plantar digital artery (PDA). On response to the warm test, PSV, EDV, and MV increased and PI and RI decreased both in DPA and PDA in these 2 groups. Moreover, the change rate in PSV, EDV, MV, PI, and RI of PDA was significantly lower in T2DM group than in control group.Color Doppler combined with a warm bath test may be used as a new method in evaluating the differences in reactivity of distal limb microvascular between healthy adults and patients with T2DM.


A Rare Case of Blastic Plasmacytoid Dendritic Cell Neoplasm Occurred in Postchemotherapy of Breast Cancer.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy that arises from plasmacytoid dendritic cells. BPDCN typically presents with skin lesions and may involve peripheral blood, bone marrow, lymph nodes, or extranodal sites. It usually arises de novo, and some BPDCN cases are associated with or develop into myeloid neoplasms. Here, we report a case of a 57-year-old female presenting with cervical lymphadenopathy and skin rashes during the COVID-19 pandemic in 2021 following multiple types of postmastectomy therapy for breast cancer. The patient was ultimately diagnosed with BPCDN by lymph node biopsy. To the best of our knowledge, this is the first case report of BPDCN occurring postchemotherapy of breast cancer.


Counseling psychology trainees' experiences with debt stress: a mixed methods examination.
Financial debt accrued by graduate psychology students has increased in recent years and is a chief concern among psychology trainees (El-Ghoroury, Galper, Sawaqdeh, & Bufka, 2012). This study examined debt stress among counseling psychology trainees using a complementary mixed methods research design. Qualitative analyses (N = 11) using the consensual qualitative research method (CQR; Hill, Thompson, & Williams, 1997; Hill et al., 2005) revealed six domains, 15 categories, and 34 subcategories. Domains included social class contributions, institutional contributions, long-term effects, coping mechanisms, personal relationships, and effect on well-being. The transactional model of stress and coping (Lazarus & Folkman, 1984) and social class worldview model (Liu, Soleck, Hopps, Dunston, & Pickett, 2004) guided quantitative analyses. Results of a path analysis (N = 285) indicated total debt and subjective social class were significant predictors of debt stress and that the relationship between debt stress and psychological distress was mediated by avoidant coping. Avoidant coping also moderated the association between debt stress and psychological distress. Results are discussed in relation to professional training and the career development of counseling psychology trainees.


Development and prospective multicenter evaluation of the long noncoding RNA MALAT-1 as a diagnostic urinary biomarker for prostate cancer.
The current strategy for diagnosing prostate cancer (PCa) is mainly based on the serum prostate-specific antigen (PSA) test. However, PSA has low specificity and has led to numerous unnecessary biopsies. We evaluated the effectiveness of urinary metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long noncoding RNA, for predicting the risk of PCa before biopsy. The MALAT-1 score was tested in a discovery phase and a multi-center validation phase. The predictive power of the MALAT-1 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. As an independent predictor of PCa, the MALAT-1 score was significantly higher in men with a positive biopsy than in those with a negative biopsy. The ROC analysis showed a higher AUC for the MALAT-1 score (0.670 and 0.742) vs. the total PSA (0.545 and 0.601) and percent free PSA (0.622 and 0.627) in patients with PSA values of 4.0-10 ng/ml. According to the decision curve analysis, using a probability threshold of 25%, the MALAT-1 model would prevent 30.2%-46.5% of unnecessary biopsies in PSA 4-10 ng/ml cohorts, without missing any high-grade cancers. Our results demonstrate that urine MALAT-1 is a promising biomarker for predicting prostate cancer risk.


Radiological management of renal trauma.
The radiological and surgical management of renal trauma patients has changed considerably in recent years, partly because of the increasing availability of high technology facilities. This article reviews the imaging examinations employed in the assessment of patients with suspected renal trauma.


Identification of vessel wall degradation in ascending thoracic aortic aneurysms with OCT.
Degradation of the wall of human ascending thoracic aorta has been assessed through Optical Coherence Tomography (OCT). OCT images of the media layer of the aortic wall exhibit micro-structure degradation in case of diseased aortas from aneurysmal vessels. The OCT indicator of degradation depends on the dimension of areas of the media layer where backscattered reflectivity becomes smaller due to a disorder on the morphology of elastin, collagen and smooth muscle cells (SMCs). Efficient pre-processing of the OCT images is required to accurately extract the dimension of degraded areas after an optimized thresholding procedure. OCT results have been validated against conventional histological analysis. The OCT qualitative assessment has achieved a pair sensitivity-specificity of 100%-91.6% in low-high degradation discrimination when a threshold of 4965.88µm(2) is selected. This threshold suggests to have physiological meaning. The OCT quantitative evaluation of degradation achieves a correlation of 0.736 between the OCT indicator and the histological score. This in-vitro study can be transferred to the clinical scenario to provide an intraoperative assessment tool to guide cardiovascular surgeons in open repair interventions.


Effect of beta-blockers on exercise physiology: implications for exercise training.
We conducted a series of studies aimed at investigating the effect of beta-blockers on exercise physiology. On the basis of these and other existing studies, it is possible to draw the following conclusions and to make the following tentative recommendations for patients engaged in exercise training who receive beta-blocker therapy: i) CAD patients treated with beta-blockers are capable of deriving the expected enhancement of cardiorespiratory fitness during training, irrespective of the type of drug used; ii) beta1-selective blockers are preferable to nonselective agents for hypertensive patients engaged in exercise training; iii) because beta1-selective blockers impair exercise tolerance in some hypertensive patients, physicians should look out for this adverse reaction and, if present, consider alternative antihypertensive therapy; iv) intrinsic sympathomimetic activity confers no advantage during exercise training; v) exercise intensity prescription for patients receiving beta-blockers should be in accordance with traditional guidelines and based on results of individualized exercise testing performed on medication; vi) exercise training is desirable during beta-blocker therapy in that it appears to offset adverse alterations in lipoprotein metabolism; and vii) nonselective beta-blockers may increase predisposition to exertional hyperthermia, and patients must therefore be encouraged to adhere strictly to accepted guidelines for heat injury prevention.


The location of cardiac vagal preganglionic motoneurones in the medulla of the cat.
1. Electrophysiological techniques have been used to locate the origin of preganglionic vagal motoneurones supplying the heart of the cat. 2. The right cardiac vagal branches were identified anatomically and their ability to slow the heart was assessed by electrical stimulation. Control experiments revealed that contamination of cardiac branches by bronchomotor and oesophageal efferent fibres was likely to be small. 3. Fifty-seven neurones in the medulla were activated antidromically on stimulating the cardiac branches at up to 5 times the threshold for cardiac slowing. They had axons with conduction velocities between 3 and 15 m/sec, corresponding to B fibres. 4. None of these were located in the region of the dorsal motor nucleus of the vagus, in spite of repeated sampling there, but all were located in the region of the nucleus ambigus. Histological examination of marked neurones (forty-six of the fifty-seven neurones) revealed that they were associated with its principal column, rostral to the obex. 5. Sampling motoneurones of the dorsal motor nucleus revealed that most sent axons down the thoracic vagus below the cardiac branches. Only three of thirty-three could be activated antidromically by high intensity stimulation of the cardiac branches, but on the basis of their thresholds and conduction velocities, it is argued that they were unlikely to be cardio-inhibitory neurones. 6. It is concluded that preganglionic cardio-inhibitory neurones arise not in the dorsal motor nucleus, but in the principal column of the nucleus ambiguus.


Synthesis and biological evaluation of sulfamoyl benzamide derivatives as selective inhibitors for h-NTPDases.
The aim of this research work is the synthesis of sulfamoyl-benzamides as a selective inhibitor for h-NTPDases. Sulfonamides are synthesized in aqueous medium from chlorosulfonylbenzoic acid while carboxamides are synthesized using carbodiimide coupling decorated with different biologically relevant substituents such as n-butyl, cyclopropyl, benzylamine, morpholine, and substituted anilines. In addition, sulfonamide-carboxamide derivatives were synthesized having the same substituents on either side. These compounds were screened against h-NTPDase activity, a main family of ectonucleotidases. Among the eight discovered isoforms of the h-NTPDases, four isoforms, h-NTPDase1, -2, -3, and -8, are involved in various physiological and pathological functions, for instance thrombosis, diabetes, inflammation, and cancer. The compound N-(4-bromophenyl)-4-chloro-3-(morpholine-4-carbonyl)benzenesulfonamide (3i) was found to be the most potent inhibitor of h-NTPDase1 with an IC50 value of 2.88 ± 0.13 μM. Similarly, the compounds N-(4-methoxyphenyl)-3-(morpholinosulfonyl)benzamide (3f), 5-(N-benzylsulfamoyl)-2-chloro-N-(4-methoxyphenyl)benzamide (3j) and 2-chloro-N-cyclopropyl-5-(N-cyclopropylsulfamoyl)benzamide (4d) reduced the activity of the h-NTPDases2 with IC50 in sub-micromolar concentrations. Against the h-NTPDase3, 3i was the potent compound with an IC50 concentration of 0.72 ± 0.11 μM. The h-NTPDase8 was selectively blocked by the most potent inhibitor 2-chloro-5-(N-cyclopropylsulfamoyl)benzoic acid (2d) with (IC50 = 0.28 ± 0.07 μM). Moreover, the molecular docking studies of the potent inhibitors showed significant interactions with the amino acids of the respective h-NTPDase homology model proteins.


A Look Back on Leadership Lessons From the Early Days of the COVID-19 Pandemic and What We Can Learn for the Future.
As the 1st community-acquired case of COVID-19 struck the Pacific Northwest, healthcare organizations prepared to respond by implementing emergency systems. Leaders navigated away from their routine daily operations to manage crisis efforts. This article highlights 6 leadership strategies used in the early days of the pandemic. Reviewing these lessons learned and revisiting the strategies used during this time will help today's leaders continue to lead through the COVID-19 pandemic and beyond.


Frequency dependence of backscatter from thin, oblique, finite-length cylinders measured with a focused transducer-with applications in cancellous bone.
A model is presented for the echo from a thin, oblique, finite-length cylinder. The echo is calculated from the line integral of the transducer directivity pattern along the cylinder axis. The model was validated with broadband pulse-echo measurements from (1) a perpendicular (to the ultrasound beam) nylon wire as a function of lateral displacement from the beam center, (2) a tilted nylon wire as a function of the angle of inclination relative to the ultrasound beam, and (3) a quasi-parallel-nylon-wire phantom, which mimicked the scattering properties of cancellous bone. The transducer directivity pattern (as a function of position and frequency) was measured with a membrane hydrophone. The model predicts an approximately cubic frequency dependence of backscatter coefficient from the phantom, as has been observed experimentally in cancellous bone. The model also predicts the relationship between the cylinder length and the exponent of a power law fit to backscatter coefficient versus frequency, which is 4 for very short (compared to a wavelength) cylinders and asymptotically approaches 3 for very long cylinders.


Retention time of digesta in the gastrointestinal tract of growing Saanen goats.
This study examined the effect of increased BW on mean retention time (MRT) of both particulate and solute marker, gastrointestinal tract (GIT) development, and fiber digestion in the whole tract of growing Saanen goats using the slaughter technique. A total of 58 Saanen goats with initial BW of 15.7 ± 0.9 kg were allocated into 9 treatments with a 3 × 3 factorial arrangement consisting of 3 sexes (female, castrated males, and intact males) and 3 slaughter weights (initial, intermediate, and final; target BW of 16, 23, and 30 kg at slaughter, respectively). They were fed twice daily (0700 and 1600 h) with the identical diets for ad libitum intake. Mean retention time of particulate matter was estimated by in situ determination of indigestible NDF (iNDF), and the MRT of solute marker was determined by Cr-EDTA. Treatment effects were evaluated in a split-plot design, with sex as the main plot and slaughter weight as the subplot. Orthogonal polynomial contrasts were used to determine linear and quadratic effects of slaughter weight, whereas the effect of sex was compared using the Tukey test. The effects of sex and sex × slaughter weight were not significant for most of variables evaluated. The results showed that DMI (% BW) linearly decreased as slaughter weight increased ( < 0.01). Generally wet weight of the total GIT tissues (% BW) decreased and digesta pool sizes (g) linearly increased with increasing slaughter weight ( ≤ 0.05). The ratio of iNDF:NDF for both ingested diet and reticulorumen digesta linearly increased as slaughter weight increased ( ≤ 0.05). The MRT of particles did not change with increasing slaughter weight ( = 0.94). Mean retention time of particulate matter linearly increased in the omasum but linearly decreased in the abomasum with increasing slaughter weight ( < 0.01). Mean retention time of solute marker in the forestomachs linearly increased with increasing slaughter weight ( < 0.01). The results revealed a decreased selectivity with increasing BW, as supported by a greater ratio of iNDF:NDF for ingested diet. Increasing BW led to neither a longer particle MRT in the reticulorumen nor a digestive advantage. The results also indicated that, on average, 91% of fiber digestion occurred in the forestomachs of the goats.


Zener tunneling in semiconductor superlattices.
Characteristics of miniband tunneling and Wannier-Stark levels in semiconductor superlattices are studied as regards their dependence on the symmetry of the unit cells and the type of miniband structure. We modify the k ⋅ p method into a k ⋅ v form and on this basis generalize the Zener formula for the inter-band tunneling in homogeneous semiconductors to the case of inter-miniband tunneling in superlattices, account being taken of the inhomogeneity of the electron effective mass. The corresponding sum rule for the effective masses in such structures is obtained. We develop a unified matrix approach for the calculation of the inter-miniband tunneling and Wannier-Stark levels in the case of an arbitrary number of minibands. We study the electric field dependence of the probability of inter-miniband tunneling for an electron transferred through the Brillouin minizone only once. The peculiarities of the inter-miniband transitions for the case where this transfer is repeated are also examined for various unit cells and miniband structures of the superlattice. In addition, we discuss mechanisms and specific features of the resonant Zener tunneling and its manifestations in electron transport.


Clinical and economic benefits of a meropenem dosage strategy based on pharmacodynamic concepts.
The clinical and economic outcomes of a meropenem dosage strategy based on pharmacodynamic concepts are retrospectively reviewed. The medical records of all patients receiving at least one day of meropenem at a large teaching hospital during 2002 were reviewed. Patients were included if they were clinically evaluable, had no prior successful antibiotic therapy, and received a meropenem dosage appropriate for renal function. Clinical outcomes were evaluated by the rate of response (days to normalization of temperature or lymphocyte count) and success rate. A cost-minimization analysis was performed from the hospital's perspective for level 1, 2, and 3 costs. The average wholesale price of meropenem for 2002 and the cost for one hospital day at our institution were used to calculate economic outcomes. Of the 136 patients identified as receiving at least one dose of meropenem, 85 met inclusion criteria, of whom 45 received meropenem 500 mg every six hours and 40 received meropenem 1000 mg every eight hours. No significant differences in demographics, site of infection, meropenem-related length of stay, or rate of response were found. Clinical success rates were similar between groups (p = 0.862). Patients taking the 500-mg regimen received less meropenem during treatment than those in the 1000-mg group (13 g versus 18 g, respectively) (p = 0.012). Median level 1 and 2 costs were significantly lower for the 500-mg regimen (p = 0.009 and p = 0.008, respectively). Level 3 costs were not significantly different. A pharmacodynamically designed meropenem dosage strategy of 500 mg every six hours yielded similar clinical outcomes to a regimen of 1000 mg every eight hours and reduced the daily drug acquisition costs associated with antibiotic therapy.


A Novel 2-Carbon-Linked Dimeric Artemisinin With Potent Antileukemic Activity and Favorable Pharmacology.
Acute myeloid leukemia (AML) remains a devastating disease, with low cure rates despite intensive standard chemotherapy regimens. In the past decade, targeted antileukemic drugs have emerged from research efforts. Nevertheless, targeted therapies are often effective for only a subset of patients whose leukemias harbor a distinct mutational or gene expression profile and provide only transient antileukemic responses as monotherapies. We previously presented single agent and combination preclinical data for a novel 3-carbon-linked artemisinin-derived dimer (3C-ART), diphenylphosphate analog 838 (ART838), that indicates a promising approach to treat AML, given its demonstrated synergy with targeted antileukemic drugs and large therapeutic window. We now report new data from our initial evaluation of a structurally distinct class of 2-carbon-linked dimeric artemisinin-derived analogs (2C-ARTs) with prior documented in vivo antimalarial activity. These 2C-ARTs have antileukemic activity at low (nM) concentrations, have similar cooperativity with other antineoplastic drugs and comparable physicochemical properties to ART838, and provide a viable path to clinical development.


A study of online consultations for paediatric renal patients in Russia.
We developed an educational website for parents of paediatric patients with kidney diseases in Russia. Parents could ask questions regarding their child's illness and submit information, including medical summaries and scanned or electronic images. A US-trained specialist in paediatric nephrology reviewed the information provided and advised about further evaluation or referral, as well as discussing possible treatment plans. In the first nine months, 141 distinct users communicated through the website. Fifty-eight percent of patients were female. An analysis of 70 cases suggested that in 45% there had been overdiagnosis of common paediatric problems, such as urinary tract infection and pyelonephritis. Users completed an anonymous satisfaction survey. The response rate was 84% (n = 59/70). The majority of respondents found the consultation useful (mean = 4.6 on a 5-point scale). The online consultation answered the questions of most respondents, provided useful information and relieved uncertainty regarding a follow-up. The majority of the respondents (>90%) confirmed that they trusted the online consultation and would recommend the technique to other parents. Online consultation for parents can provide reliable information that results in improved parental satisfaction and education. This approach may be useful in improving care and providing patient education in underserved areas in the USA and elsewhere.


Hyperoxaluria After Renal Transplantation.
Primary hyperoxaluria is a rare autosomal recessive disorder, characterised by precipitation of insoluble oxalate crystals in the joints, kidneys, heart, eyes, skin, nerves, and bone marrow. The patients of primary oxaluria usually present with renal stone/nephrocalcinosis, and isolated kidney transplantation should not be done in these patients. We present a case report of 31-year lady with acute graft dysfunction due to oxaluria with no history of nephrolithiasis/nephrocalcinosis prior to renal transplantation.


Pharmacokinetics and pharmacodynamics of irbesartan in healthy subjects.
The safety, pharmacokinetics, and pharmacodynamics of single and multiple doses of the angiotensin II (AII) AT1 blocker irbesartan were assessed in healthy subjects. In this single-center, placebo-controlled, double-blind within dose group, sequential, dose-ascending study, 48 men were randomized to receive irbesartan at doses of 150 mg, 300 mg, 600 mg, or 900 mg daily. Subjects received a single dose of irbesartan (n = 9 per group) or placebo (n = 3 per group), followed by 3 days of placebo, and then multiple doses of irbesartan or placebo once daily for 7 days. The values for plasma area under the concentration-time curve (AUC) of irbesartan were dose proportional up to 600 mg. There were no significant differences between the dose groups in time to maximum concentration (tmax) or half-life (t1/2) after single and multiple doses. After multiple doses, urinary recovery was significantly lower in the 600-mg and 900-mg dose groups compared with the 150-mg and 300-mg dose groups. Steady-state concentrations of irbesartan were achieved within 3 days of administration with no clinically important accumulation. Irbesartan produced dose-dependent increases in plasma renin activity and AII levels. Irbesartan was well tolerated at doses from 150 mg to 900 mg daily; a maximally tolerated dose was not reached. Modest decreases in blood pressure without orthostatic symptoms were observed at irbesartan doses of 300 mg or higher. These results demonstrated the dose-proportionality of irbesartan 150 mg to 600 mg and indicated that doses up to 900 mg daily were well tolerated.


Factors controlling sorption of prosulfuron by variable-charge soils and model sorbents.
Prosulfuron [1-(4-methoxy-6-methyltriazin-2-yl)-3-[2-(3,3,3-trifluoropropyl) phenylsulfonyl]-urea), a relatively new sulfonylurea herbicide, is a weak acid (pK(a) 3.76), and therefore, will undergo pH-dependent speciation and sorption. Understanding prosulfuron sorption in soils is important for predicting its environmental fate. Soil and solution factors controlling sorption were investigated by measuring prosulfuron sorption on five model sorbents (amorphous silica, alpha-alumina, CaSWy1 montmorillonite, commercial humic acid, and anion exchange resin) and 10 variable-charge soils from CaCl(2) and Ca(H(2)PO(4))(2) solutions as a function of pH and ionic strength. Anion exchange of prosulfuron accounted for up to 82% of overall sorption in the pH range from 3 to 7. The relative importance of anion exchange to prosulfuron sorption was positively correlated to the ratio of anion and cation exchange capacities. Comparison between organic carbon (OC)-normalized sorption (K(oc)) versus pH for humic acid and variable-charge soils show similar trends with sorption decreasing with increasing pH. However, K(oc) values estimated from variable-charge soils in the lower pH range where anion exchange has the greatest contribution to sorption was almost one log unit greater than that estimated from humic acid clearly exemplifying the impact of anion exchange. Similarity in K(oc)-pH curves for humic acid and variable-charge soils may result from the fact that (i) cation exchange capacity increases with increasing OC content, thus effective anion exchange capacity is reduced; and (ii) the relative contribution of hydrophobic and hydrophilic sorption mechanisms was fairly constant. Given that both hydrophilic and hydrophobic sorption of prosulfuron decrease with increasing pH, addition of fertilizer and lime amendments may enhance the potential for off-site leaching of recently applied acidic pesticides.


Pulmonary arterial hypertension associated to connective tissue diseases.
Pulmonary arterial hypertension is a well-known complication of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, mixed connective tissue diseases, and to a lesser extent, rheumatoid arthritis, dermatopolymyositis and primary Sjögren's syndrome. In these patients, pulmonary hypertension may occur in association with left heart disease, interstitial fibrosis or as a result of a isolated pulmonary arteriopathy. The incidence of pulmonary arterial hypertension in the limited form of systemic sclerosis is about 10%. The pathophysiologic mechanisms leading to pulmonary arterial hypertension remain unknown. Symptoms and clinical presentation are very similar to idiopathic pulmonary arterial hypertension but mortality was confirmed to be higher. Echocardiography is the reference investigation for the detection of pulmonary arterial hypertension but the results should be confirmed by right heart catheterization. Treatment appears more complex as compared to idiopathic pulmonary arterial hypertension. Intravenous epoprostenol therapy has been shown to be effective in a special trail. Also, the endothelin receptor antagonists bosentan and sitaxentan, the phosphodyesterase-type-5 sildenafil and subcutaneous treprostinil have shown favourable results.


Hypothermia-Induced Ubiquitination of Voltage-Dependent Anion Channel 3 Protects BV2 Microglia Cells From Cytotoxicity Following Oxygen-Glucose Deprivation/Recovery.
Background: Hypothermia attenuates microglial activation and exerts a potential neuroprotective effect against cerebral ischemic-reperfusion (I/R) injury. However, the underlying mechanism remains to be elucidated. In this in vitro study, a model of oxygen-glucose deprivation, followed by recovery (OGD/R), was used to investigate whether hypothermia exerts anti-inflammatory and anti-apoptosis properties via enhanced ubiquitination and down-regulation of voltage-dependent anion channel 3 (VDAC3) expression. Methods: BV2 microglia were cultured under OGD for 4 h following reperfusion with or without hypothermia for 2, 4, or 8 h. M1 and M2 microglia markers [inducible nitric oxide synthase (iNOS) and arginase (Arg)1] were detected using immunofluorescence. The levels of pro-inflammatory cytokines [tumor necrosis factor (TNF) α, interleukin (IL)-1β], and anti-inflammatory factor (IL-10) were determined using enzyme-linked immunosorbent assay (ELISA). Mitochondrial membrane potential (ΔΨm) was assayed by JC-1 staining using a flow cytometer. Expression of caspase-3, cleaved caspase-3, and VDAC3 were assessed using western blot analysis. The cellular locations and interactions of ubiquitin and VDAC3 were identified using double immunofluorescence staining and immunoprecipitation (IP) assay. Also, the level of the VDAC3 mRNA was determined using a quantitative polymerase chain reaction (qPCR). Results: Hypothermia inhibited the OGD/R-induced microglia activation and differentiation into the M1 type with pro-inflammatory effect, whereas it promoted differentiation to the M2 type with anti-inflammatory effect. Hypothermia attenuated OGD/R-induced loss of Δψm, as well as the expression of apoptosis-associated proteins. Compared to normothermia, hypothermia increased the level of ubiquitinated VDAC3 in the BV2 microglia at both 2 and 8 h of reperfusion. Furthermore, hypothermia did not attenuate VDAC3 mRNA expression in OGD/R-induced microglia. Conclusions: Hypothermia treatment during reperfusion, attenuated OGD/R-induced inflammation, and apoptosis in BV2 microglia. This might be due to the promotion of VDAC3 ubiquitination, identifying VDAC3 as a new target of hypothermia.


Mechanisms of endoplasmic-reticulum export of glycine transporter-1 (GLYT1).
The GLYT1 (glycine transporter-1) regulates both glycinergic and glutamatergic neurotransmission by controlling the reuptake of glycine at synapses. Trafficking to the cell surface of GLYT1 is critical for its function. In the present paper, by using mutational analysis of the GLYT1 C-terminal domain, we identified the evolutionarily conserved motif R(575)L(576)(X(8))D(585) as being necessary for ER (endoplasmic reticulum) export. This is probably due to its capacity to bind Sec24D, a component of the COPII (coatomer coat protein II) complex. This ER export motif was active when introduced into the related GLYT2 transporter but not in the unrelated VSVG (vesicular-stomatitis virus glycoprotein)-GLYT1 protein in which this motif was mutated but was not transported to the plasma membrane, although this effect was rescued by co-expressing these mutants with wild-type GLYT1. This behaviour suggests that GLYT1 might form oligomers along the trafficking pathway. Cross-linking assays performed in rat brain synaptosomes and FRET (fluorescence resonance energy transfer) microscopy in living cells confirmed the existence of GLYT1 oligomers. In summary, we have identified a motif involved in the ER exit of GLYT1 and, in analysing the influence of this motif, we have found evidence that oligomerization is important for the trafficking of GLYT1 to the cell surface. Because this motif is conserved in the NSS (sodium- and chloride-dependent neurotransmitter transporter) family, it is possible that this finding could be extrapolated to other related transporters.


Conventional fascial technique versus mesh repair for advanced pelvic organ prolapse: Analysis of recurrences in treated and untreated compartments.
117 women with severe pelvic organ prolapse (POP; stage > 2) were enrolled to elucidate a 24-month outcome of POP surgery, using conventional or mesh repair with 3 techniques. 59 patients underwent conventional repair and 58 underwent mesh repair. Two types of mesh were used: a trocar-guided transobturator polypropylene (Avaulta, Bard Inc.) and a porcine dermis mesh (Pelvisoft, Bard Inc.). Women with recurrences, who underwent previous unsuccessful conventional repair, were randomised. Primary outcome was the evaluation of anatomic failures (prolapse stage > 1) in treated and untreated compartments. Anatomic failure was observed in 11 of 58 patients (19%; CI 8.9-29) in the mesh group and in 16 of 59 patients (27.1%; p value = 0.3) in the conventional group. 9 of 11 failures in the mesh group (15.5%; CI 6.2-24.8) were observed in the untreated compartment (de novo recurrences), 14.3% in Pelvisoft and 16.7% in Avaulta arm, while only 1 recurrence in the untreated compartment (1.7%) was observed in the conventional group (odds ratio 10.6, p = 0.03).


Stratification of hypertension and SARS-CoV-2 infection by quantitative NMR spectroscopy of human blood serum.
Diagnostic approaches like the nuclear magnetic resonance spectroscopy (NMR) based quantification of metabolites, lipoproteins, and inflammation markers has helped to identify typical alterations in the blood serum of COVID-19 patients. However, confounders such as sex, and comorbidities, which strongly influence the metabolome, were often not considered. Therefore, the aim of this NMR study was to consider sex, as well as arterial hypertension (AHT), when investigating COVID-19-positive serum samples in a large age-and sex matched cohort. NMR serum data from 329 COVID-19 patients were compared with 305 healthy controls. 134 COVID-19 patients were affected by AHT. These were analyzed together with NMR data from 58 hypertensives without COVID-19. In addition to metabolite, lipoprotein, and glycoprotein data from NMR, common laboratory parameters were considered. Sex was considered in detail for all comparisons. Here, we show that several differences emerge from previous NMR COVID-19 studies when AHT is considered. Especially, the previously described triglyceride-rich lipoprotein profile is no longer observed in COVID-19 patients, nor an increase in ketone bodies. Further alterations are a decrease in glutamine, leucine, isoleucine, and lysine, citric acid, HDL-4 particles, and total cholesterol. Additionally, hypertensive COVID-19 patients show higher inflammatory NMR parameters than normotensive patients. We present a more precise picture of COVID-19 blood serum parameters. Accordingly, considering sex and comorbidities should be included in future metabolomics studies for improved and refined patient stratification. Due to metabolic similarities with other viral infections, these results can be applied to other respiratory diseases in the future.


Associations between Stress, Anxiety, Depression and Sleep Quality among Healthcare Students.
Stress, anxiety, and depression among students have many negative health consequences and may predispose students to poor sleep quality; therefore, this research aimed to investigate the perceived stress, anxiety, and depression and their relation to the level of sleep quality among healthcare students. A cross-sectional study using a validated survey was conducted among Saudi healthcare students from different regions during the period from 26 September 2022 to 30 October 2022. The Pittsburgh Sleep Quality Index (PSQI) was utilized to assess sleep quality. PSPP Statistical Analysis Software version 1.2.0 was used for all statistical analyses. 701 respondents participated in this research; the response rate was 73.8%. About 60% of the study sample was female, and the average age was 20.9 years. 80.3% of students have poor sleep quality; the participants' mean sleeping hours per night was 6.81 ± 1.88 h. About three-quarters of students (72.9%) perceive themselves as stressed. A significant positive correlation was observed between sleep quality and perceived stress (r-value = 0.363), anxiety (r-value = 0.387), and depression (r-value = 0.347). Poor sleep quality was more likely among those with stress than those without stress (AOR = 1.79; 95% CI 1.07, 2.99) and two times more likely among students with cases of anxiety than those without anxiety (AOR = 2.07; 95% CI 1.10, 3.94). Our study highlights the high prevalence of poor sleep quality, anxiety, depression, and stress among healthcare students in Saudi Arabia. Students' reported stress, anxiety, and residence region were associated with poor sleep quality. These results imply the necessity of regular screening and appropriate intervention for sleep problems, stressors, and anxiety among healthcare students.


Cell lipid biology in infections: an overview.
Lipids are a big family of molecules with a vast number of functions in the cell membranes, within the cytoplasm, and extracellularly. Lipid droplets (LDs) are the most common storage organelles and are present in almost every tissue type in the body. They also have structural functions serving as building blocks of cellular membranes and may be precursors of other molecules such as hormones, and lipoproteins, and as messengers in signal transduction. Fatty acids (FAs), such as sterol esters and triacylglycerols, are stored in LDs and are used in β-oxidation as fuel for tricarboxylic acid cycle (TCA) and adenosine triphosphate (ATP) generation. FA uptake and entrance in the cytoplasm are mediated by membrane receptors. After a cytoplasmic round of α- and β-oxidation, FAs are guided into the mitochondrial matrix by the L-carnitine shuttle system, where they are fully metabolized, and enter the TCA cycle. Pathogen infections may lead to impaired lipid metabolism, usage of membrane phospholipids, and LD accumulation in the cytoplasm of infected cells. Otherwise, bacterial pathogens may use lipid metabolism as a carbon source, thus altering the reactions and leading to cellular and organelles malfunctioning. This review aims to describe cellular lipid metabolism and alterations that occur upon infections.


Leukotrienes and their antagonists in allergic disorders.
Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of allergic rhinitis and asthma. Strategies for inhibition of cysteinyl leukotriene receptors and inhibition of 5-lipoxygenase activity. The leukotrienes antagonists, with particular reference to asthma and allergic rhinitis, is reviewed in this paper. In studies in asthmatic patients, these compounds can inhibit bronchoconstriction in response to exercise, aspirin and allergen. Results from clinical studies using receptor antagonists, such as LY-171883, SK&F-104353, ICI-204219, ONO-1078, MK-751, MK-0679, demonstrate beneficial effects, with improvement in symptoms and forced expiratory volume in one second (FEV1), and a reduction in the use of beta 2-adrenergic relief medication. NZ-107 was studied for its effect on airway inflammation caused by intratracheal injection of LTB4 or IL-5, or by inhalation of PAF, and by cell activation. Analysis of the BAL fluid revealed that both induced eosinophilia and neutrophilia were suppressed. Surprisingly, although PAF and superoxide generation were inhibited in macrophages and eosinophils, NZ-107 had no effect on neutrophil activation. U-75302 was studied in guinea pigs and inhibited LTB4 induced chemotaxis of eosinophils in vitro and antigen-induced lung eosinophilia in vivo. Further studies are needed to clarify the exact mechanism by which these compounds provide beneficial effects.


2-D clinorotation alters the uptake of some nutrients in Arabidopsis thaliana.
Future long-term spaceflight missions rely on bioregenerative life support systems (BLSS) in order to provide the required resources for crew survival. Higher plants provide an essential part since they supply food and oxygen and recycle carbon dioxide. There are indications that under space conditions plants might be inefficient regarding the uptake, transport and distribution of nutrients, which in turn affects growth and metabolism. Therefore, Arabidopsis thaliana (Col-0) seeds were germinated and grown for five days under fast clinorotation (2-D clinostat, 60rpm) in order to simulate microgravity. Concentrations of ten different nutrients (potassium, sulfur, phosphorus, calcium, sodium, magnesium, manganese, iron, zinc, and boron) in shoots of plants grown under reduced and normal (1g) gravity conditions were compared. A protocol was developed for the determination of different nutrients by means of inductively coupled plasma optical emission spectrometry (ICPOES), flame emission spectrometry and spectrophotometry. The concentrations of boron and sulfur were significantly decreased in clinorotated shoots, while the concentration of sodium was elevated, suggesting that altered gravity conditions differentially affected nutrient uptake. Possible mechanisms for such effects include reduced transpiration, altered expression of channels or transporters and direct effects on nutrient assimilation. The observed nutrient imbalances might have a negative impact on plant growth and nutritional quality during prolonged space missions.


Localization and structural analysis of the ribosomal RNA operons of Rhodobacter sphaeroides.
We have identified, cloned and sequenced the three ribosomal RNA (rRNA) operons (rrn) present in the facultative photoheterotroph Rhodobacter sphaeroides. DNA sequence analysis has identified the 16S, 23S, and 5S rRNAs, two tRNAs (ile and ala) in the spacer region between the 16S and 23S rRNAs, and an f-met tRNA immediately following the 5S rRNA gene of all three operons. Physical mapping, genetic analysis, and Southern hybridization data indicate that rrnA is contained on a large chromosome and rrnB and rrnC are contained on a second smaller chromosome. These findings are discussed in relation to the origins of diploidy.


Guided Immediate Implant Placement with Wound Closure by Computer-Aided Design/Computer-Assisted Manufacture Sealing Socket Abutment: Case Report.
Digital technology has been widely used in the field of implant dentistry. From a surgical standpoint, computer-guided surgery can be utilized to enhance primary implant stability and to improve the precision of implant placement. From a prosthetic standpoint, computer-aided design/computer-assisted manufacture (CAD/CAM) technology has brought about various restorative options, including the fabrication of customized abutments through a virtual design based on computer-guided surgical planning. This case report describes a novel technique combining the use of a three-dimensional (3D) printed surgical template for the immediate placement of an implant, with CAD/CAM technology to optimize hard and soft tissue healing after bone grafting with the use of a socket sealing abutment.


Interventions for treating catheter-related bloodstream infections in people receiving maintenance haemodialysis.
Patients with kidney failure require vascular access to receive maintenance haemodialysis (HD), which can be achieved by an arteriovenous fistula or a central venous catheter (CVC). CVC use is related to frequent complications such as venous stenosis and infection. Venous stenosis occurs mainly due to trauma caused by the entrance of the catheter into the venous lumen and repeated contact with the vein wall. A biofilm, a colony of irreversible adherent and self-sufficient micro-organisms embedded in a self-produced matrix of exopolysaccharides, is associated with the development of infections in patients with indwelling catheters. Despite its clinical relevance, the treatment of catheter-related bloodstream infections (CRBSIs) in patients receiving maintenance HD remains controversial, especially regarding catheter management. Antibiotic lock solutions may sterilise the catheter, treat the infection and prevent unnecessary catheter procedures. However, such treatment may also lead to antibiotic resistance or even clinical worsening in certain more virulent pathogens. Catheter removal and delayed replacement may remove the source of infection, improving infectious outcomes, but this approach may also increase vascular access stenosis, thrombosis or both, or even central vein access failure. Catheter guidewire exchange attempts to remove the source of infection while maintaining access to the same vein and, therefore, may improve clinical outcomes and preserve central veins for future access. To assess the benefits and harms of different interventions for CRBSI treatment in patients receiving maintenance HD through a permanent CVC, such as systemic antibiotics alone or systemic antibiotics combined with either lock solutions or catheter guidewire exchange or catheter replacement. We searched the Cochrane Kidney and Transplant Register of Studies up to 21 December 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomised controlled trials (RCTs) and quasi-RCTs evaluating the management of CRBSI in permanent CVCs in people receiving maintenance HD. Two authors independently selected studies for inclusion, assessed their risk of bias, and performed data extraction. Results were expressed as risk ratios (RR) or hazard ratios (HR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with their 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE. We identified two RCTs and one quasi-RCT that enrolled 760 participants addressing the treatment of CRBSIs in people (children and adults) receiving maintenance HD through CVC. No two studies compared the same interventions. The quasi-RCT compared two different lock solutions (tissue plasminogen activator (TPA) and heparin) with concurrent systemic antibiotics. One RCT compared systemic antibiotics alone and in association with an ethanol lock solution, and the other compared systemic antibiotics with different catheter management strategies (guidewire exchange versus removal and replacement). The overall certainty of the evidence was downgraded due to the small number of participants, high risk of bias in many domains, especially randomisation, allocation, and other sources of bias, and missing outcome data. It is uncertain whether an ethanol lock solution used with concurrent systemic antibiotics improved CRBSI eradication compared to systemic antibiotics alone (RR 1.61, 95% CI 1.16 to 2.23) because the certainty of this evidence is very low. There were no reported differences between the effects of TPA and heparin lock solutions on cure rates (RR 0.92, 95% CI 0.74 to 1.15) or between catheter guidewire exchange versus catheter removal with delayed replacement, expressed as catheter infection-free survival (HR 0.88, 95% CI 0.43 to 1.79). To date, no results are available comparing other interventions. Outcomes such as venous stenosis and/or thrombosis, antibiotic resistance, death, and adverse events were not reported. Currently, there is no available high certainty evidence to support one treatment over another for CRBSIs. The benefit of using ethanol lock treatment in combination with systemic antibiotics compared to systemic antibiotics alone for CRBSIs in patients receiving maintenance HD remains uncertain due to the very low certainty of the evidence. Hence, further RCTs to identify the benefits and harms of CRBSI treatment options are needed. Future studies should unify CRBSI and cure definitions and improve methodological design.


Fetal renal dysplasia: sonographic evaluation.
In an attempt to predict histologic fetal renal dysplasia among fetuses with obstructive uropathy, three antenatal sonographic features (presence of renal cortical cysts, echogenicity of renal parenchyma, and degree of hydronephrosis) were studied. Identification of renal cortical cysts in the kidneys of fetuses with obstructive uropathy enabled accurate prediction of renal dysplasia. Of 49 fetal kidneys with obstructive uropathy, all 15 kidneys with sonographically visible cortical cysts had severe but not necessarily lethal dysplasia (accuracy of positive prediction = 100%). Of 15 obstructed but nondysplastic fetal kidneys, none had sonographically visible cysts (specificity = 100%). The absence of fetal renal cysts on antenatal sonography, however, did not exclude the presence of dysplasia. Assessment of the echogenicity of renal parenchyma and the degree of hydronephrosis are of only limited value in predicting whether an obstructed fetal kidney will show histologic dysplasia.


A new species of Pseudione Kossmann, 1881 (Isopoda, Cymothoida, Bopyridae) parasitizing the lobster Nephropsis aculeata Smith, 1881 (Decapoda, Astacidea, Nephropidae) in the Southwestern Atlantic.
A new species of Pseudione Kossmann, 1881 is described from two parasitized specimens of the clawed lobster Nephropsis aculeata Smith, 1881, collected from Brazilian waters in the southwestern Atlantic. It is the second species of the genus from Brazil and is the fourth species parasitizing nephropid lobsters in the world.


Machine Learning Enables Prediction of Cardiac Amyloidosis by Routine Laboratory Parameters: A Proof-of-Concept Study.
(1) Background: Cardiac amyloidosis (CA) is a rare and complex condition with poor prognosis. While novel therapies improve outcomes, many affected individuals remain undiagnosed due to a lack of awareness among clinicians. This study was undertaken to develop an expert-independent machine learning (ML) prediction model for CA relying on routinely determined laboratory parameters. (2) Methods: In a first step, we developed baseline linear models based on logistic regression. In a second step, we used an ML algorithm based on gradient tree boosting to improve our linear prediction model, and to perform non-linear prediction. Then, we compared the performance of all diagnostic algorithms. All prediction models were developed on a training cohort, consisting of patients with proven CA (positive cases, n = 121) and amyloidosis-unrelated heart failure (HF) patients (negative cases, n = 415). Performances of all prediction models were evaluated on a separate prognostic validation cohort with 37 CA-positive and 124 CA-negative patients. (3) Results: Our best model, based on gradient-boosted ensembles of decision trees, achieved an area under the receiver operating characteristic curve (ROC AUC) score of 0.86, with sensitivity and specificity of 89.2% and 78.2%, respectively. The best linear model had an ROC AUC score of 0.75, with sensitivity and specificity of 84.6 and 71.7, respectively. (4) Conclusions: Our work demonstrates that ML makes it possible to utilize basic laboratory parameters to generate a distinct CA-related HF profile compared with CA-unrelated HF patients. This proof-of-concept study opens a potential new avenue in the diagnostic workup of CA and may assist physicians in clinical reasoning.


Biological and clinical effects of the oral immunomodulator 3,6-bis(2-piperidinoethoxy)acridine trihydrochloride in patients with malignancy.
CL 246,738 is a synthetic heterocyclic of the acridine class that has immunomodulating, interferon (IFN)-inducing, and antitumor activity by the oral route in mice. We have completed a phase I ascending dose trial to determine the maximum tolerated oral dose and biologic modifying effects. Twenty-three patients received CL 246,738 orally at five dose levels, escalating from 5 to 50 mg/kg. The major side effects were gastrointestinal disturbances such as nausea, vomiting, and diarrhea. No hematologic, hepatic, or symptomatic dose-limiting toxicities were encountered. The mean half-life of CL 246,738 in whole blood was at least 300 h and remained relatively constant over the dose range studied. Higher doses resulted in increased whole blood levels. Biologic response modification included stimulation of the IFN-induced proteins, 2',5'-oligoadenylate synthetase and beta 2-microglobulin, at higher doses of CL 246,738, and enhanced T-cell proliferation to alloantigens at lower doses. Increases in lymphocytes bearing the Leu-7 phenotypic marker were observed and some patients had enhanced natural killer (NK) cell cytotoxicity. Enhanced NK cell cytotoxicity was demonstrated in vitro. Thus, CL 246,738 was orally relatively well tolerated and has immunomodulating properties in humans.


High similarity between bacterioneuston and airborne bacterial community compositions in a high mountain lake area.
The bacterioneuston (bacteria inhabiting the air-water interface) is poorly characterized and possibly forms a unique community in the aquatic environment. In high mountain lakes, the surface film is subjected to extreme conditions of life, suggesting the development of a specific and adapted bacterioneuston community. We have studied the surface film of a remote high mountain lake in the Pyrenees by cloning the PCR-amplified 16S rRNA gene and comparing with bacteria present in underlying waters (UW), and airborne bacteria from the dust deposited on the top of the snow pack. We did not detect unusual taxa in the neuston but rather very common and widespread bacterial groups. Betaproteobacteria and Actinobacteria accounted for >75% of the community composition. Other minor groups were Gammaproteobacteria (between 8% and 12%), Alphaproteobacteria (between 1% and 5%), and Firmicutes (1%). However, we observed segregated populations in neuston and UW for the different clades within each of the main phylogenetic groups. The soil bacterium Acinetobacter sp. was only detected in the snow-dust sample. Overall, higher similarities were found between bacterioneuston and airborne bacteria than between the former and bacterioplankton. The surface film in high mountain lakes appears as a direct interceptor of airborne bacteria useful for monitoring long-range bacterial dispersion.


Multichannel detectors for profile measurements in clinical proton fields.
Two beam profile measurement detectors have been developed at Indiana University Cyclotron Facility to address the need for a tool to efficiently verify dose distributions created with active methods of clinical proton beam delivery. The multipad ionization chamber (MPIC) has 128 ionization chambers arranged in one plane and is designed to measure lateral profiles in fields up to 38 cm in diameter. The MPIC pads have a 5 mm pitch for fields up to 20 cm in diameter and a 7 mm pitch for larger fields, providing the accuracy of field size determination about 0.5 mm. The multilayer ionization chamber (MLIC) detector contains 122 small-volume ionization chambers stacked at a 1.82 mm step (water-equivalent) for depth-dose profile measurements. The MLIC detector can measure profiles up to 20 cm in depth, and determine the 80% distal dose fall-off with about 0.1 mm precision. Both detectors can be connected to the same set of electronics modules, which comprise the detectors' data acquisition system. The detectors have been tested in clinical proton fields produced with active methods of beam delivery such as uniform scanning and energy stacking. This article describes detector performance tests and discusses their results. The test results indicate that the MPIC and MLIC detectors can be used for dosimetric characterization of clinical proton fields. The detectors offer significant time savings during measurements in actively delivered beams compared with traditional measurements using a water phantom.


Effects of two combinations of triple antibiotic paste used in endodontic regeneration on root microhardness and chemical structure of radicular dentine.
We investigated the effects of triple antibiotic paste (TAP) and modified triple antibiotic paste (MTAP) concentrations on the microhardness and chemical structure of radicular dentine. Human root cylinders were instrumented and randomized into four treatment groups and an untreated control group. Two treatment groups received 1 g/mL TAP or MTAP, and the other two treatment groups received 1 mg/mL methylcellulose-based TAP or MTAP. Cylinders were stored at 100% relative humidity for 4 weeks. Each root cylinder was subjected to a microhardness test before and after treatment. Different sets of radicular dentine specimens were treated as mentioned previously, and were examined using attenuated total reflection Fourier transform infrared spectroscopy. All treatment groups showed significant reductions in microhardness of roots when compared to untreated control roots at 1,000 and/or 500 µm from the pulp-dentine interface. However, 1 mg/mL methylcellulose-based antibiotics caused significantly less reduction in microhardness when compared to 1 g/mL antibiotics. In addition, 1 g/mL TAP and DAP caused significantly lower phosphate/amide I ratios when compared to other groups. The use of 1 mg/mL methylcellulose-based TAP and MTAP may minimize the reduction in microhardness of roots compared with the currently used 1 g/mL concentration of these antibiotics.


Long-term behavioural and neuroendocrine effects of perinatal activation or blockade of CB1 cannabinoid receptors.
The present work studied the long-term effects of chronic perinatal manipulation of cannabinoid CB1 receptors in male and female rats. Perinatal activation of cannabinoid CB1 receptors by chronic administration of delta9-tetrahydrocannabinol at different doses (0.1, 0.5, 2 mg/kg, p.o.) induced sexually dimorphic behavioural changes in adulthood, altering habituation of locomotion, immobility and exploratory activity. These behavioural effects were also accompanied by alterations in corticosterone levels in the adult period. Prenatal blockade of CB1 receptors by chronic administration of 3 mg/kg (s.c.) of SR141716A decreased immobility behaviour in male and female animals, without any significant changes in corticosterone plasma levels. Cannabinoid CB1 receptors appear to play an important role in the ontogeny of psychomotor behaviours, and activation or blockade of these receptors during stages of plasticity, such as the prenatal or perinatal periods, can induce long-term effects, as shown by sexually dimorphic changes in behavioural patterns in adulthood.


[The expression of Treg/Th17 cells related transcription factors and cytokines in PBMCs and plasma in patients with allergic rhinitis].
To investigate the changes of Treg/Th17 cells related transcription factors (FOXP3, RORC) and cytokines (TGF-beta, IL-17) in the peripheral blood in patients with allergic rhinitis. Use visual analogue scale (VAS) to assess the allergic rhinitis severity of patients. Eighteen patients with allergic rhinitis and 12 healthy control subjects were consecutively enrolled. Peripheral blood samples were obtained from all patients and healthy control subjects (after prick test). The mRNA expressions of key transcription factors (RORC, FOXP3) in PBMCs were measured by RT-PCR, and the concentrations of TGF-beta, IL-17 in plasma were measured by ELISA. Patients with moderate/severe persistent rhinitis have a VAS of 8.5 +/- 0.8, and total patients have a VAS of 6.2 +/- 1.6. Compared with healthy control subjects, the mRNA expressions of FOXP3 and the concentrations of TGF-beta in plasma were significantly lower in patients with allergic rhinitis (P < 0.01) while the mRNA expressions of RORC and the concentrations of IL-17 in plasma were significantly higher in allergic rhinitis group (P < 0.01). The imbalance of Treg/Th17 cells existed in allergic rhinitis patients, which may contribute to the proceeding of allergic rhinitis.


[Expression of KAI1, MRP-1, and FAK proteins in lung cancer detected by high-density tissue microarray].
The genesis, development, invasion, and metastasis of tumor are closely correlate with alterations of multi-genes. At present, the roles of Kang-ai-1 (KAI1), motility-related protein-1 (MRP-1), and focal adhesion kinase (FAK) in lung cancer have seldom been reported. This study was designed to investigate the roles of KAI1, MRP-1, and FAK in tumorigenesis and development of lung cancer, and their values in diagnosis and predicting the prognosis of lung cancer. The expression of KAI1, MRP-1, and FAK proteins in a high-density tissue microarray containing 240 spots were detected by SP immunohistochemistry. The positive rates of KAI1 and MRP-1 were significantly lower in primary lung cancer than in normal lung tissue (25.9% vs. 100%, 42.6% vs. 100%, P<0.05). The positive rate of FAK was significantly higher in primary lung cancer than in normal lung tissue (44.4% vs. 10.0%, P<0.05). The expression of KAI1, FAK, and MRP-1 in primary lung cancer had no correlation with age and gender of the patients, and macroscopic and histological type of tumor, but had correlations with tumor differentiation, clinical stage, and lymph node metastasis. In addition, the expression of MRP-1 had correlation with histological type of tumor; the positive rate of MRP-1 was significantly lower in small cell lung cancer than in non-small cell lung cancer (0 vs. 50.0%, P<0.05). KAI1 expression was negatively correlated to FAK expression (rs=-0.458, P<0.05); MRP-1 expression was positively correlated with KAI1 expression (rs=0.535, P<0.05), and negatively correlated with FAK expression (rs=-0.438, P<0.05). The abnormal expression of KAI1, MRP-1, and FAK proteins are related to invasion and metastasis of lung cancer. Combined detection of the 3 proteins may be useful in predicting the development and prognosis of lung cancer.


Influence of helical twisting power on the photoswitching behavior of chiral azobenzene compounds: applications to high-performance switching devices.
Five photochromic chiral azobenzene compounds and one nonphotochromic chiral compound were synthesized and characterized by IR, 1H NMR spectroscopy, and elemental analysis. Cholesteric liquid crystalline phases were induced by mixing of the nonphotochromic chiral compound and one of the photochromic chiral azobenzene compounds in a host nematic liquid crystal (E44). The helical pitch of the induced cholesteric phase was determined by Cano's wedge method and the helical twisting power (HTP) of each sample was thus determined. The helical twisting powers of azobenzene compounds were decreased upon UV irradiation, due to trans-->cis photoisomerization of azobenzene molecules. Among the azobenzene compounds synthesized in our study, Azo-5, with isomannide (radical) as chiral photochromic dopant, showed the highest HTP and contrast ratio (Tmax/Tmin). Photoswitching between compensated nematic phase and cholesteric phase was achieved through reversible trans<-->cis photoisomerization of the chiral azobenzene molecules through irradiation with UV and visible light, respectively. Transmission rates (contrast ratios) increased with decreasing helical pitch length in the induced cholesteric phase. The influence of helical twisting power on the photoswitching behavior of chiral azobenzene compounds is discussed in detail.


Density functional theory and surface enhanced Raman spectroscopy characterization of novel platinum drugs.
There is considerable interest in the development of novel platinum-based anticancer drugs that overcome the disadvantages associated with the widely used drug cisplatin, which are its inactivity against some types of tumors and its toxic side effects. In this study we show the suitability of normal Raman spectroscopy (NRS) and surface enhanced Raman spectroscopy (SERS), assisted by density functional theoretical (DFT) calculations, for the characterization of Pt complexes. The Pt complexes studied include the established drugs cisplatin and carboplatin, as well as five novel Pt complexes with anticancer activity. DFT calculations at the B3LYP/LanL2DZ level are a good prediction of the experimental NRS spectra of small and medium sized Pt complexes. The use of SERS allows the investigation of Pt complexes at physiological concentrations, and the binding strengths of the different ligands can be determined. The formation of positively charged hydrolysis products may be necessary for SERS activity. The exiting group in the hydrolysis reaction can be identified.


[Diffusion/spreading of malaria in the Apuo-Lunensis region (northwest of Tuscany)].
Evidence of malaria fevers in the antiquity may be found in the writings of Herodotus (regarding the Nilo Valley) or in Latin authors (regarding the south land of Rome); successive reclaiming of lands by the Roman Empire diminished the incidence of malaria, but in the medieval time the absence of care regarding drainage of swampi plains caused the outbreak of the disease. In the XIX century lands were claimed, but very slowly for example in the Apuo-Lunensis region, so that experts of public health were often consulted by local governments. District physicians affirmed the origin of malaria from the local environment, and the local Governor De Volo drained the land about the Magliano river by filling of marshes, malaria was strongly reduced, coming at the end of the century for few years due to breaking of banks of the Frigido river.


Design and control of six degree-of-freedom active vibration isolation table.
A six-axis active vibration isolation system (AVIS) is designed by using the direct driven guide and ball contact mechanisms in order to have no cross-coupling between actuators. The point contact configuration gives an advantage of having an easy assembly of eight voice coil actuators to an upper and a base plate. A voice coil actuator is used since it can provide a large displacement and sufficient bandwidth required for vibration control. The AVIS is controlled considering the effect of flexible vibration mode in the upper plate and velocity sensor dynamics. A loop shaping technique and phase margin condition are applied to design a vibration controller. The performances of the AVIS are investigated in the frequency domain and finally validated by comparing with the passive isolation system. The scanning profiles of the specimen are compared together by using the atomic force microscope. The robustness of the AVIS is verified by showing the impulse response.


Buerger's disease and anticardiolipin antibodies: a worse prognosis?
The case of a 26-year-old male chronic smoker is reported, who had thrombotic incidences on three occasions in both upper and lower limbs over a 10-month period. Laboratory examinations, including hematologic studies and creatinine, cholesterol, and glucose levels, were normal. However, IgG and IgM anticardiolipin antibodies were detected. Duplex ultrasonography confirmed deep venous thrombosis in both lower limbs (two occurrences) and computer tomography depicted an inferior cava vein thrombosis. The patient fulfilled all of Shionoya's criteria for Buerger's disease, thus suggesting an association between anticardiolipin antibodies and this disease.


Safety and efficacy of transurethral pneumatic lithotripsy for bladder calculi in children.
To determine the safety and efficacy of transurethral pneumatic lithotripsy for bladder calculi in children. The study included 100 children up to 15 years of age undergoing pneumatic cystolithoclast for bladder stones. The descriptive study was conducted from September 2006 to February 2007 at the Sindh Institute of Urology and Transplantation, Karachi. The inclusion criteria was children up to 15 years of age with a bladder stone of up to 3cm, pre-operative negative urine culture, no coagulopathy and fit for general anaesthesia. An X-ray and ultrasound of Kidney and Urinary Bladder (KUB) was mandatory. The procedure was done under general anaesthesia with a single dose of pre-operative antibiotic. A mini-scope of 4FR or a semi-rigid ureteroscope of 7/8.5 FR with pneumatic wolf lithoclast was used for the fragmentation of stones. Duration of procedure, any per-operative and post-operative complications and the duration of hospital stay were recorded. Post-operatively, the patient underwent ultrasound Kidney and Urinary Bladder at the first follow-up to assess stone clearance after one week. Mean patients age was 4.95 +/- 3.3 years. The male-to-female ratio was 11.5: 1 The mean hospital stay was 9.2 +/- 2.5 hours. The mean operating time was 25 (10 -65) minutes. Ten (10%) patients developed minor complications out of which 5 (5%) developed haematuria and 4 (4%) developed difficulty in passing urine. One (1%) of the patients developed post-operative retention of urine. All the patients were stone-free after the procedure. The transurethral pneumatic lithoclast is very effective and safe in children with bladder stones up to 3cm.


Good work ability among unemployed individuals: Association of sociodemographic, work-related and well-being factors.
The aims of this study were to describe the perceived work ability of unemployed individuals and to explore the association between perceived good work ability and sociodemographic, work-related and well-being factors. The data were derived from the Finnish Regional Health and Well-being Study (ATH) collected by postal and Internet-based questionnaires in 2014-2015. The random sample was selected from the Finnish National Population Register. The present study includes data from unemployed or laid-off respondents ( n=1975) aged 20-65 years. Logistic regression was used in the statistical analysis. Perceived work ability was measured with the Work Ability Score. Factors significantly associated with good work ability were having young children living in the household, short-term unemployment, low or moderate physical strain in most recent job, moderate mental strain in most recent job, satisfaction with most recent job, good self-rated health and good quality of life. Good self-rated health (odds ratio=10.53, 95% confidence interval 5.90-18.80) was the most substantial factor in the multivariate model. The findings provide further evidence on the factors related to good work ability of the unemployed. These factors should be considered when designing interventions for promoting work ability and to minimise the harmful effects of long-term unemployment.


Resistant metastatic penile carcinoma and response to biochemotherapy with paclitaxel and epidermal growth factor receptor monoclonal antibody, nimotuzumab.
Carcinoma penis is one of the common malignancies in developing world especially among rural population. Multimodality treatment with surgery, radiation and chemotherapy for advanced penile carcinoma with groin nodal metastasis is crucial to optimise the outcome. Cisplatin, fluorouracil, methotrexate, vinorelbine, bleomycin and paclitaxel are the common chemotherapeutic agents used along with local therapy. Paucity of data to show superiority of one chemotherapeutic regime over another and only modest response to any combination chemotherapy. Progression of disease after surgery, radiation and chemotherapy is associated with poor outcome and quality of life. Nimotuzumab, Anti EGFR monoclonal antibody, along with paclitaxel in our case of resistant metastatic penile carcinoma has shown good symptomatic palliation and clinical response.


Identification of Postblast Residues by DART-High Resolution Mass Spectrometry Combined with Multivariate Statistical Analysis of the Kendrick Mass Defect.
The coupling of an atmospheric pressure ionization source (Direct Analysis in Real Time, DART) and a high-resolution mass spectrometer (Orbitrap) has enabled the rapid and efficient analysis of a variety of energetic formulations. This approach was used to generate mass spectra for 83 plastic explosives and polymer samples in less than 2 min per sample. To manually interpret and identify all of the constituent polymers and other interesting features in the acquired mass spectra is a tedious and time-consuming challenge. Instead, a methodology based on the systematic calculation of Kendrick mass defects (KMDs) was developed and implemented. Its application allowed the identification of the polymeric support present in each energetic formulation. The presence of polyisobutylene in PG2 has been confirmed thanks to this approach, and a mixture of polyisobutylene, polybutadiene, and polystyrene has been confirmed in the Semtex 10 formulation. The developed methodology has also permitted the observation of changes that occur to the polymeric composition of these formulations after a blast. It appears that the most adequate way to describe post blast polymer samples is that they are less oxygenated and, above all, more unsaturated than the original starting material. These conclusions were deduced with the aid of principal component analysis, which served to establish the main factors that differentiate the samples.


Challenges in the diagnosis and management of IBD: a sub-Saharan African perspective.
With the exception of South Africa, inflammatory bowel disease (IBD) has long been considered uncommon in sub-Saharan Africa (SSA) with a dearth of peer-reviewed publications from the subcontinent. This most likely reflects underreporting as some cases may be missed due to the high burden of infectious diseases which may closely mimic IBD. In addition, many countries in SSA have limited endoscopic capacity, inadequate access to diagnostic imaging and a notable scarcity of histopathologists, radiologists and gastroenterologists. Beyond these obstacles, which significantly impact patient care, there are many other challenges in SSA, particularly the unavailability of key IBD therapies. In this review, we discuss barriers in diagnosing and managing IBD in SSA, as well as some of the initiatives currently in place to address these short comings.


Oral vaccination of BALB/c mice with Salmonella enterica serovar Typhimurium expressing Pseudomonas aeruginosa O antigen promotes increased survival in an acute fatal pneumonia model.
Pseudomonas aeruginosa is a leading cause of nosocomial pneumonia. We compared the efficacies of oral and intraperitoneal (i.p.) vaccinations of BALB/c mice with attenuated Salmonella enterica serovar Typhimurium SL3261 expressing P. aeruginosa serogroup O11 O antigen to protect against P. aeruginosa infection in an acute fatal pneumonia model. Oral and i.p. vaccines elicited O11-specific serum immunoglobulin G (IgG) antibodies, but IgA was observed only after oral immunization. Challenge of orally vaccinated mice with an O11 strain (9882-80) at 6 and 12 times the 50% lethal dose showed increased survival in mice that received the vaccine compared to phosphate-buffered saline (PBS)- and vector-treated controls; no difference in survival was seen with a heterologous strain, 6294 (serogroup O6). In addition, significant protection against 9882-80 was not observed in i.p. vaccinated animals. Bronchoalveolar lavage fluid taken from immunized mice harbored O11-specific IgA and IgG in orally immunized mice but only modest levels of IgG in i.p. vaccinated mice. To correlate protection, opsonophagocytosis assays were performed with pooled sera from orally immunized animals. Efficient killing of five O11 clinical isolates was observed, while no killing was noted with 6294, indicating that the recombinant SL3261 oral vaccine induces an O11-specific reaction. We next determined the ability of orally vaccinated animals to clear bacteria from their lungs. Following P. aeruginosa challenge, the numbers of viable bacteria were significantly fewer in orally vaccinated animals than in PBS- and vector-treated controls. Our results suggest that oral immunization with recombinant SL3261 is efficacious in protection against pneumonia caused by P. aeruginosa.


Lymphangiomyomatosis and angiomyolipoma: closely related entities characterized by hamartomatous proliferation of HMB-45-positive smooth muscle.
Angiomyolipoma is a hamartomatous condition which can occur as a component of the tuberous sclerosis complex. Lymphangiomyomatosis, another hamartomatous lesion occurring predominantly in the lungs, has long been suspected to be related to angiomyolipoma and tuberous sclerosis because of occasional clinical associations. We undertook this study to provide further support for the close relationship between these two entities. Five cases of lymphangiomyomatosis and 20 case of angiomyolipoma were retrieved for histological review and immunohistochemical studies. The antibodies used were anti-muscle specific actin (HHF-35), anti-desmin (D33) and anti-melanoma (HMB-45). Lesions featuring smooth muscle proliferation were used as controls. The proliferated smooth muscle cells in both lymphangiomyomatosis and angiomyolipoma were much plumper and paler or even clear, when compared with the deeply eosinophilic cytoplasm of the normal spindly smooth muscle cells and those of leiomyomas. Their nuclei were round to oval and pale rather than elongated and dark. Cells with bizarre nuclei were commoner in angiomyolipoma (18/20 cases) than lymphangiomyomatosis (1/5). In 12 cases of angiomyolipoma there were foci indistinguishable from lymphangiomyomatosis, i.e. plump spindle cells arranged in short fascicles around ramifying endothelium-lined spaces. All five cases of lymphangiomyomatosis stained for muscle-specific actin, desmin and HMB-45. For angiomyolipomas, the positivity rates for these markers were: 20/20, 17/20 and 18/20, respectively, including one case that was negative for both desmin and HMB-45. The various smooth muscle proliferations and tumours selected as controls were uniformly HMB-45 negative. The distinctive cytological features, morphological overlap and immunophenotypic profile all support a close relationship between lymphangiomyomatosis and angiomyolipoma, which probably represent different morphological manifestations of hamartomatous proliferation of a peculiar form of HMB-45-positive smooth muscle.


Conformations and vibrational spectra of a model tripeptide: change of secondary structure upon micro-solvation.
Mid-infrared (IR) hole burning spectra of the model tripeptide Z-Aib-Pro-NHMe (Z = benzyloxycarbonyl) in gas phase and its micro-clusters with one and two methanol molecules are presented. To establish a relation between experimental spectra and the underlying conformations, calculations at the DFT [B3LYP/6-311++G(d,p)] level of theory are performed. In particular, the intra-peptide and the peptide-methanol hydrogen bonds can be identified from spectral shifts in the amide I, II, and III regions. While the unsolvated tripeptide as well as its one-methanol cluster prefer a gamma-turn structure, a beta-turn structure is found for the two-methanol cluster, in agreement with previous condensed phase studies. Comparison of measured and simulated spectra reveals that the favorable methanol binding sites are at the head and tail parts of the tripeptide. The interconversions between gamma-turn and beta-turn structures are governed by potential barriers below 10 kJ mol(-1) inside one of the low energy basins of the potential energy surface.