The RNA interference (RNAi) technique is a new modality for cancer therapy, and several candidates are being tested clinically. Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of ‘personalized medicine’.
Technologies on theranostic nanomedicines has been discussed. We designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90 nm, bright green fluorescence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. This chapter presents an over view of the current status of translating the RNAi cancer therapeutics in the clinic, a brief description of the biological barriers in drug delivery, and the roles of imaging in aspects of administration route, systemic circulation, and cellular barriers for the clinical translation of RNAi cancer therapeutics, and with partial content for discussing the safety concerns. Finally, we focus on imaging-guided delivery of RNAi therapeutics in preclinical development, including the basic principles of different imaging modalities, and their advantages and limitations for biological imaging. With growing number of RNAi therapeutics entering the clinic, various imaging methods will play an important role in facilitating the translation of RNAi cancer therapeutics from bench to bedside.
Bacterial vaginosis (BV) is associated with adverse pregnancy outcomes with various treatment options.
Objective: To compare the efficacy and effect on pregnancy outcome of Metronidazole and Clindamycin in women with bacterial vaginosis in Port Harcourt, Nigeria.
Methodology: Randomized controlled study of 136 pregnant women diagnosed with BV at the University of Port Harcourt Teaching Hospital. A structured proforma was used to obtain socio-demographic characteristics and other relevant data. Treatment was with either oral Metronidazole or oral Clindamycin for seven days. A secondary test and evaluation of the effect on adverse pregnancy outcomes were determined. Data analysis was done using the SPSS statistical package version 22.0
Results: BV prevalence was 23%, with similar cure rates with both medications. The failure rates of clindamycin and metronidazole were 10.4% and 13% respectively (p = 0.639). The mean gestational age at delivery in the metronidazole treated group was 38.67 weeks ± 1.69 compared to 38.68 weeks ± 1.64 in the oral clindamycin group (p = 0.96). Pre-labour rupture of membranes and preterm delivery rates with both medications were similar (p = 0.73; OR 1.3; 95% CI 0.3-4.9) and (p = 0.73; OR 1.3; 95% CI 0.3-4.9) respectively.
Conclusion: Both medications have comparable efficacy and similar pregnancy outcomes in the treatment of bacterial vaginosis in low-risk asymptomatic pregnant Nigerian women and thus can be used interchangeably.
Context: Perioperative management of morbidly obese patients undergoing bariatric surgery is challenging. Lacking standardized perioperative protocols, complication rates may be high. This retrospective study aims to quantify the incidence of significant blood pressure decreases on induction of anesthesia and intraoperative hypoxemia, before implementation of a standardized protocol designed for bariatric surgery.
Design: Retrospective, observational study.
Setting: A 250-bed county hospital in northern Sweden.
Subjects: 219 morbidly obese patients (body mass index > 35 kg/m2) who underwent bariatric surgery between 2003 and 2008.
Main outcome measures: Incidence of systolic blood pressure (SAP) falls to less than 70% of the preoperative baseline during induction of anesthesia and incidence of perioperative hypoxemia.
Results: The incidence of confirmed SAP falls to below 70% of baseline at induction of anesthesia was 56.2% (n = 123/219). This incidence rose with increasing age (p < 0.001) but not with body mass index (BMI). 3.7% (n = 8/219) of cases were marked as difficult intubations. A transient period of hypoxemia was observed in 6.8% (n = 15/219) and was more common with increasing BMI (p = 0.005). Fourteen different drug combinations were used in the study population. Of those administered an induction anesthetic drug, 72.6% (n = 159/193) were given an overdose when calculated by lean body weight, but this did not correlate significantly to SAP falls (p = 0.468).
Conclusion: The incidence of a significant blood pressure fall upon induction of anesthesia was common. The incidence of airway and ventilation problems were low. Overdosing of anesthetics and excessive variation in applied anesthesia methods were found.
Background: The aim of the study was to evaluate radiographic features of systemic sclerosis-associated interstitial lung disease.
Patients and methods: 116 patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) from 2010 to 2019 comprised our retrospective study. All patients were subject to high resolution computed tomography (HRCT). ILD patterns were classified into 7 patterns as IIPs and analyzed with pathology. We chose two staging method and two semi-quantitative score methods to evaluate the HRCT performance and analyzed with pulmonary function tests.
Results: Ground-glass opacities were the most common presentation on HRCT, followed by interlobular septal thickening, reticular opacities, intralobular interstitial thickening; honeycombing, traction bronchiectasis and nodules can also be observed. The most common pattern of SSc-ILD was nonspecific interstitial pneumonia (NSIP), secondly was UIP. There was no difference in ILD pattern between HRCT and pathology, and revealed a high congruence. The four HRCT evaluating methods presented in this study all had significant relationships with PETs.
Conclusion: The most common pattern of SSc-ILD was nonspecific interstitial pneumonia (NSIP). The ILD patterns of HRCT coincide very well with histology, and will replace pathology as the gold standard for diagnosis and evaluation of SSc-ILD.
Background: Orthoses need to support physiotherapy as well as surgical treatment. Related to patient’s rehabilitative goals and pathological gait pattern, orthotists have to produce an orthoses that using an adjustable ankle joint system with preloaded disc springs can store the energy brought in by the body weight and produce a tuning effect on patient’s gait and sense of balance. The purpose of this study was to establish how a personalized proprioceptive individualized rehabilitative treatment could influence the functional response of different AFOs (Ankle Foot Orthoses) in a cohort of patients affected by neurological gait pattern.
Methods: Five patients affected by different neurological gait pattern and volunteered to participate to this study were recruited. The comparative spatio-temporal and functional effect on gait pattern of 3 types of AFOs was investigated under 4 study conditions: 1) without AFO or free-walk (FW); 2) wearing a Codivilla spring, 3) wearing a carbon unjointed AFO (“Toe-Off”); 4) wearing an innovative carbon-kevlar dynamic joint DAFO (DAFONS=Dynamic Ankle Foot Orthoses with Neuroswing). In line with our rehabilitative model, patients underwent to a weekly treatment session, 80 minutes duration per session, for 4 weeks. Evaluation was made before (time T3=time of recruitment) and after our individualized rehabilitative treatment course (time T4=1 month from T3) by using: a. G-Walk sensor (by BTS) spatio-temporal measures in different gait performances; b. clinical/functional outcome measures (Modified Ashworth Scale or MAS for the affected upper and lower limb; Medical Research Council or MRC; orthostatic stability evaluation by using the Berg Balance Scale or BBS).
Findings: A comparative analysis of clinical and instrumental data, performed in the pre-defined four investigational conditions, showed:
√ a statistical insignificant change of MRC and MAS scales at time T4, with a significance trend outcome observed at the same time by using the Wilcoxon Signed Rank Test
√ a statistical significant difference between test duration (sec) by using Toe-Off vs DAFONS and by using Codivilla spring vs Toe-Off
√ a statistical significant increase of the stride length on the left side (% cycle length) by using DAFONS compared to Toe-Off for patient P1, P3 and P5 with a parameter decrease by using DAFONS compared to Codivilla spring and Toe-Off use for patient P2
√ a statistical significant correlation between BBS trend and test duration (sec) by using Codivilla spring at time T3 and T4
√ a statistical significant correlation between the BBS trend and the double gait support duration on the right side (% cycle) with number of left step cycles by using DAFONS at time T3 and T4
√ in a comparative post-treatment visual gait analysis a modification of each patient’s static and dynamic postural assessment by using 3 different types of orthoses
Interpretation: In line with our study design we noted at the end of the proposed rehabilitative treatment an amelioration of gait quality with the use of DAFONS in all those patients (P1, P3 and P5) who showed a neurocognitive competence with a related functional grade of neurorehabilitative re-learning attitude of the physiological gait pattern and with a compromised perceptive control of gait and core stability. The proprioceptive profile of our rehabilitative program could promote the pro-adaptive and facilitation properties of a personalized gait control, induced by an innovative dynamic ankle foot orthoses with a modulable ankle joint system called Neuroswing. In the daily clinical practice, the personalized integration of a neurorehabilitative program and DAFONS can perform an individualized peripheral neuro-facilitation of gait cycle (peripheral perceptive facilitation), a neurorehabilitative re-learning process of physiological gait pattern (peripheral assisted neuroplasticity facilitation DAFONS induced) and an increase of patient’s motor abilities and quality of life in all daily performances.
Background: We report our experience with management and treatment of pregnant women who were admitted at our institution for snake envenomation.
Methosd: We reviewed the charts and recorded the management, treatment, and outcome of 51 pregnant women admitted to our high-risk obstetric service with a diagnosis of snakebite.
Results: One patient experienced spontaneous abortion, 2 had intrauterine fetal death due to placental abruption, 2 delivered malformed babies, 1 had premature birth of twins with low birthweight. There were no maternal deaths.
Conclusion: Snake-venom poisoning in pregnancy is a complex medical emergency that involves complications at the site of the bite and may also involve dysfunction of multiple organ systems in both mother and fetus.
Aims: Histological diagnostic criteria are used for the assessment of the degree of dysplasia and hence the risk of cancer progression for premalignant lesions. Clonal changes in the form of hyperorthokeratosis and hyperchromasia that are sharply demarcated from adjacent areas are not currently part of the criterion for dysplasia diagnosis. The objective of this study was to determine whether such clonal change should be regarded as a diagnostic feature for dysplasia. The following histological conditions were used to define such change: (1) hyperorthokeratosis; (2) hyperchromatism but no other features of dysplasia; (3) sharp margin demarcation from adjacent area by both the hyperorthokeratosis and hyperchromasia (clonal change), and (4) no prominent rete ridges, marked acanthosis or heavy inflammation. Lesions fitting these criteria were termed orthokeratotic lesions with no dysplasia.
Methods: Patients from a population-based longitudinal study with more than 10 years of follow up were analyzed. Of the 214 patients with primary oral premalignant lesions, 194 had mild or moderate dysplasia (dysplasia group) and 20 fit the criteria for orthokeratotic lesions without dysplasia (orthokeratotic with no dysplasia group). The two groups were compared for their cancer risks using clinical (site and toluidine blue), histological (nuclear phenotype score), and molecular criteria (loss of heterozygosity) and by outcome (progression).
Results and conclusions: The lesions from orthokeratotic with no dysplasia group showed a similar cancer risk (clinical, histological and molecular risk) and time to progression as the dysplastic lesions. We recommend that the clonal change should be included as a criterion for dysplasia diagnosis
Background: Pre-eclampsia is a frequent and serious pregnancy complication contributing for the increasing maternal morbi-mortality rates. This study was designed to evaluate the effect of calcium supplementation during pregnancy, on the incidence of pre-eclampsia and eclampsia among primigravid women.
Method: In a hospital-based, opened, randomized and controlled clinical trial carried out in the city of Yaounde, 70 women were randomized to either 1.5 g daily calcium supplements (n = 35) or vitamins at the same time (n = 35) from 20 weeks gestation till delivery. Were included all singleton healthy, primigravid women who offered their signed inform consent and were excluded, all women with any chronic condition. Primary outcomes were pre-eclampsia and eclampsia.
Results: No significant difference was observed between the two study groups with respect to the baseline characteristics obtained at enrollment. We recorded a sevenfold decrease in the incidence of preeclampsia in the calcium group (RR = 0.26, CI 0.06 – 0.44, p = 0.024). The onset of pre-eclampsia was delayed 3 weeks in the calcium group. Meanwhile the mean diastolic blood pressure at delivery was of no significant difference (p = 0.126), the mean systolic blood pressure at delivery however, presented a significant difference between both groups (p = 0.009).
Conclusion: A 1.5 g daily calcium supplementation of healthy normotensive primigravid women during pregnancy seems to be effective in reducing the incidence of pre-eclampsia.
Andreas Suhartoyo Winarno*, Lukas Schloesser, Frederic Dietzel, Percy Balan, Thomas Hoehn, Monika Hampl and Tanja Natascha Fehm
Published on: 16th December, 2019
Deliveries prior to 28 weeks’ gestation (extreme preterm birth) pose a global health concern, according to the World Health Organization (WHO). Extreme preterm birth is associated with several complications in the newborn and management in neonatal intensive care unit would incur high expenses. In parallel, advancements in in vitro fertilization will give an opportunity for women to conceive in cases of ovarian failure. At the same time, health providers also encourage patients to receive more than one embryo simultaneously during an embryo transfer. Here we report a case of a patient in coma condition of triplet pregnancy, post ovum donation with three-embryo transfer. Following stabilization, cranial computed tomography (CCT) was performed. The result showed bleeding in the brainstem and into intraventricular spaces at 25+4 gestation weeks. Furthermore, ICH during pregnancy is considered as a rare case in obstetrical field, especially involving the brainstem. This could lead to life-threatening conditions and serious disability in the future. On the fifth day of hospitalization, she suffered from pneumonia and pulmonary edema. On the eight day (26+5 gestations weeks), an emergency caesarean section was performed due to fully dilated of the cervix with breech presentation of all fetuses. Mother and the children survived with some non-life-threatening disabilities.
This is the very first case reported of intracerebral hemorrhage in the brainstem in triplet pregnancy after receiving ovum donation. Heterologous conception could be an iceberg phenomenon of gestational complications among the population. Reproductive tourism could still become greater in the future.
Background: Leiomyoma itself is not a rare disease, but it is rarely found intravascularly.
Case presentation: A 54-year old female sought medical help after noticing her leg being swelling. A diagnosis of deep vein thrombosis (DVT) was made and antithrombotic treatment was given after her initial imaging exam. Several days later, a contrast CT and sequential pathology revealed the real diagnosis was intravascular leiomyoma. The patient was discharged after a successful surgery.
Conclusion: Intravascular leiomyoma should not be confused with DVT.
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