Engineering Novel Amphiphilic Platinum(IV) Complexes to Co-Deliver Cisplatin and Doxorubicin.

In this study, we report a novel platinum-doxorubicin conjugate that demonstrates superior therapeutic indices to cisplatin, doxorubicin, or their combination, which are commonly used in cancer treatment. This new molecular structure (1) was formed by conjugating an amphiphilic Pt(IV) prodrug of cisplatin with doxorubicin. Due to its amphiphilic nature, the Pt(IV)-doxorubicin conjugate effectively penetrates cell membranes, delivering both cisplatin and doxorubicin payloads intracellularly. The intracellular accumulation of these payloads was assessed using graphite furnace atomic absorption spectrometry and fluorescence imaging. Since the therapeutic effects of cisplatin and doxorubicin stem from their ability to target nuclear DNA, we hypothesized that the amphiphilic Pt(IV)-doxorubicin conjugate (1) would effectively induce nuclear DNA damage toward killing cancer cells. To test this hypothesis, we used flow the cytometric analysis of phosphorylated H2AX (γH2AX), a biomarker of nuclear DNA damage. The Pt(IV)-doxorubicin conjugate (1) markedly induced γH2AX in treated MDA-MB-231 breast cancer cells, showing higher levels than cells treated with either cisplatin or doxorubicin alone. Furthermore, MTT cell viability assays revealed that the enhanced DNA-damaging capability of complex 1 resulted in superior cytotoxicity and selectivity against human cancer cells compared to cisplatin, doxorubicin, or their combination. Overall, the development of this amphiphilic Pt(IV)-doxorubicin conjugate represents a new form of combination therapy with improved therapeutic efficacy.

SERS detection of R6G based on a novel graphene oxide/silver nanoparticles/silicon pyramid arrays structure.

We present a novel surface-enhanced Raman scattering (SERS) substrate based on graphene oxide/silver nanoparticles/silicon pyramid arrays structure (GO/Ag/PSi). The SERS behaviors are discussed and compared by the detection of R6G. Based on the contrast experiments with PSi, GO/PSi, Ag/PSi and GO/AgA/PSi as SERS substrate, the perfect bio-compatibility, good homogeneity and chemical stability were confirmed. We also calculated the electric field distributions using Finite-difference time-domain (FDTD) analysis to further understand the GO/Ag/PSi structure as a perfect SERS platform. These experimental and theoretical results imply that the GO/Ag/PSi with regular pyramids array is expected to be an effective substrate for label-free sensitive SERS detections in areas of medicine, food safety and biotechnology.

[A New Approach to the Depletion of Albumin and Immunoglobulin G from Human Serum].

The use of proteomic analysis to find potential diagnostic biomarkers is limited by the presence of serum albumin (HSA) and immunoglobulin (IgG) at high concentrations in patients' blood; these substances impede the detection of serum proteins with similar molecular weights. Recombinant HSA- and IgG-binding polypeptides are used as ligands in creating sorbents for complete removal of the proteins by affinity chromatography. The binding specificity of the sorbents for HAS and IgG is higher than that of the conventionally used antibodies. A composite sorbent enabling the depletion of HSA and IgG from serum by single-step affinity chromatography is obtained. The. developed sorbents were used to prepare serum for proteomic analysis.

Sapphire-based graphene saturable absorber for long-time working femtosecond lasers.

We report a long-time working femtosecond laser using metal-free sapphire-based graphene as a saturable absorber (SA). The sapphire-based graphene yielded excellent nonlinear saturable absorption properties and was demonstrated to be suitable as an SA for an ultrafast solid-state laser. Stable mode-locked pulses of 325 fs were obtained at a central wavelength of 1032 nm with a repetition rate of 66.3 MHz. At pump power of 8.23 W the average output power was 1.78 W and the highest pulse energy reached 26.8 nJ with a peak power of 72.6 kW. Our work opens up a facile route for making reliable graphene SA in the mode-locking technique and also displays an exciting prospect in making low-cost and ultrafast lasers.

Facile synthesis of graphene on dielectric surfaces using a two-temperature reactor CVD system.

Direct deposition of graphene on a dielectric substrate is demonstrated using a chemical vapor deposition system with a two-temperature reactor. The two-temperature reactor is utilized to offer sufficient, well-proportioned floating Cu atoms and to provide a temperature gradient for facile synthesis of graphene on dielectric surfaces. The evaporated Cu atoms catalyze the reaction in the presented method. C atoms and Cu atoms respectively act as the nuclei for forming graphene film in the low-temperature zone and the zones close to the high-temperature zones. A uniform and high-quality graphene film is formed in an atmosphere of sufficient and well-proportioned floating Cu atoms. Raman spectroscopy, scanning electron microscopy and atomic force microscopy confirm the presence of uniform and high-quality graphene.

Perioperative pain relief by a COX-2 inhibitor affects ileal repair and provides a model for anastomotic leakage in the intestine.

The authors examined the potential of the cyclooxygenase 2 (COX-2) inhibitor carprofen to reproducibly induce anastomotic leakage. In experiment 1, an anastomosis was constructed in both ileum and colon of 20 rats, and they were given carprofen (5 mg/kg subcutaneously every 24 hours) or buprenorphine (0.02 mg/kg subcutaneously every 12 hours). In another 20 rats an anastomosis was constructed in either ileum or colon, and all received carprofen (experiment 2). Animals were sacrificed after 3 days. In experiment 1, the ileal dehiscence rate was 60% in the carprofen group and 0% in the buprenorphine group (P = .0108). Colonic anastomoses in both groups remained patent. In experiment 2, the anastomotic leakage rate was 80% in ileum and 0% in colon. Thus, COX-2 inhibitors can severely interfere with intestinal healing, particularly in the ileum. Perioperative administration of carprofen yields a unique model for anastomotic leakage, which allows translational research on the effectiveness of perisuture line reinforcement.

Citrobacter freundii-associated osteomyelitis and thromboembolic events following Moderna COVID-19 vaccination: a rare case report from Nepal.

Introduction: Vaccination against coronavirus disease 2019 (COVID-19) is essential for controlling the ongoing cases of this disease. Citrobacter infections of the bones and joints are extremely uncommon. Thromboembolism and deep vein thrombosis (DVT) are very rare complications. Case presentation: The authors present a rare case of osteomyelitis, septic arthritis, deep venous thrombosis, and pulmonary embolism in a 15-year-old previously healthy boy occurring shortly after receiving the second dose of the Moderna COVID-19 vaccine. He experienced pain, swelling in the right leg, shortness of breath, and fever, followed by chest pain and leg edema. Treatment included anticoagulation, ketorolac for pain management, antipyretics, and intravenous antibiotics (Tazobactam/Piperacillin, Linezolid, Clindamycin) for osteomyelitis. Discussion: The risk of COVID-19 vaccine-related thrombotic events is minimal. Thrombotic events reported among mRNA is very rare. Citrobacter freundii bone and joint infections are very rare, accounting for a small percentage of cases. Some documented cases include cefotaxime-resistant strains causing necrotizing fascitis and osteomyelitis, including postarthroplasty infections. Due to the diverse range of susceptibility patterns and the widespread occurrence of drug resistance, personalized treatment based on culture and sensitivity testing is recommended. However, in rare cases, severe complications like DVT and joint infections associated with Citrobacter infection may occur and should be reported to the vaccine adverse events reporting system. Conclusion: Administering the COVID-19 vaccine to enhance natural antibodies is crucial, despite the low risk of infection, thromboembolism, and DVT. Healthcare providers should stay vigilant about adverse effects postvaccination and promptly report those cases.

Diagnostic challenges in tuberculous meningitis: a case report with negative genexpert result.

Introduction: Tuberculous meningitis (TBM) is a severe form of tuberculosis affecting the meninges, primarily caused by Mycobacterium tuberculosis. Diagnosis of TBM poses numerous challenges due to its nonspecific clinical presentation and the limitations of diagnostic tests like GeneXpert. Case presentation: The authors report a case of a 22-year-old female from Eastern Nepal presenting with acute-onset fever, headache, vomiting, and neck pain. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, low glucose levels, and cobweb coagulum indicative of TBM. However, the GeneXpert test revealed negative results. Discussion: In resource-limited settings like Nepal, where access to GeneXpert MTB/Rif is limited, CSF analysis and clinical algorithms play a crucial role in diagnosing TBM. Relying solely on GeneXpert results may lead to false negatives, so a high level of suspicion based on patient risk factors is essential. Prompt initiation of empirical antitubercular therapy is vital for a favorable outcome in TBM cases. Conclusion: Negative MTB PCR results from CSF can be misleading in diagnosis of tubercular meningitis. Therefore, comprehensive evaluations, including detailed patient history, physical examination, and CSF fluid analysis, are crucial in high tuberculous prevalence countries to ensure accurate and timely diagnosis.

[Peculiarities of the biology and parasite fauna of juvenile Atlantic salmon (Salmo salar L.) in the Pista River (White Sea Basin), according to the Gyrodactylus salaris infestation].

Juvenile salmon Salmo salar m. sebago Girard from the Pista River system (the White Sea Basin) was investigated. The data on species composition and occurrence peculiarities of Gyrodactylus salaris Malmberg, 1957 are given. This monogenean is the alien species for the river system and it is recorded for the first time. It is shown that the distribution of the parasite abundance is can be described as the negative binomial distribution; variations of its parameters (k and p) were also characterized. Parasitological data obtained, as well as the data describing the characteristics of growth and age structure of juvenile salmon population, suggest the potential influence of G. salaris infection on the degree of survival of fishes in the lake-river system examined.

Gabapentin for the treatment of carpal tunnel syndrome: a randomized controlled trial.

OBJECTIVE: Based on its efficacy in treating neuropathic pain, gabapentin may be effective for the treatment of carpal tunnel syndrome (CTS). The purpose of this study was to evaluate the efficacy of gabapentin for symptom relief in CTS. METHODS: We conducted a randomized, double-blinded, placebo-controlled trial recruiting patients with newly diagnosed idiopathic CTS of more than a period of three months. Diagnosis was based on characteristic symptoms with electrophysiological confirmation. Patients were randomly assigned to an active group receiving gabapentin (starting dose 300 mg once daily to a target of 900 mg daily) or a placebo group. Primary end-point was the global symptom score (GSS), which was measured at baseline, two, and eight weeks. RESULTS: There was no significant difference in baseline variables between the two treatment groups. Hundred and forty patients were enrolled in the study, of whom 71 were randomly assigned to gabapentin group and 69 assigned to placebo group. Both gabapentin and placebo produced significant improvement in symptoms at two and eight weeks. The GSS at 2 and 8 weeks was 16.4 (SD 9.4) and 13.4 (SD 9.7), respectively, in the active group versus 14.9 (SD 9.0) and 12.5 (SD 8.9) in the control group (P < 0.01). But by eight weeks, the mean reduction in symptom severity of patients on gabapentin [-10.4 (SD 10.8)] was not significant when compared with placebo [-8.7 (SD 8.1), P < 0.39]. Adverse events were not severe and included dizziness, somnolence, and headache. CONCLUSIONS: Gabapentin did not produce a significant reduction in symptom severity compared with placebo over an eight-week period.

Cerebral venous thrombosis secondary to ovarian hyperstimulation syndrome.

We report a case of a woman who underwent in-vitro fertilisation embryo transfer treatment for infertility and developed an acute stroke (left hemiparesis and headache). The stroke was caused by cerebral venous thrombosis due to ovarian hyperstimulation syndrome. We review the current background about this uncommon disorder.

Long-term outcomes of ischemic stroke patients with concurrent intracranial and extracranial stenoses and ischemic heart disease.

BACKGROUND AND PURPOSE: Coexisting ischemic heart disease (IHD) and concurrent atherosclerosis of intracranial and extracranial vessels is common in Asians. This study aims to investigate the long-term outcomes of ischemic stroke patients with concurrent stenoses and IHD. METHODS: This was a prospective cohort study in Hong Kong. Consecutive Chinese patients with acute ischemic stroke underwent MRI, magnetic resonance angiography and carotid duplex sonography. RESULTS: A total of 428 patients were included. The mean follow-up period was 65 months (up to 87 months). Ninety-three patients (22%) died of any cause and 104 patients (22%) suffered from nonfatal vascular events. Fifty-four patients (13%) had IHD. Among them, 27 patients (50%) had concurrent stenoses. In patients with concurrent stenoses and IHD, only 3 (11%) were free of death and recurrent vascular events. Eight (30%) had recurrent nonfatal stroke, 7 (26%) had nonfatal myocardial infarct (MI) and 11 (41%) died, 6 (22%) of them due to fatal MI. The overall 5-year cumulative rates of mortality, recurrent vascular events and combined poor outcomes were 21, 23 and 43%, respectively. In patients with concurrent stenoses and IHD, these rates were 40, 50 and 83%, respectively. More deaths (log rank: 6.56; p = 0.01), recurrent vascular events (log rank: 25.24; p < 0.001) and poor outcomes (log rank: 27.50; p < 0.001) were found among patients with concurrent stenoses and IHD. CONCLUSIONS: Ischemic stroke patients with concurrent stenoses and IHD had high risks of death and recurrent vascular events. Future studies on aggressive medical therapy and early cardiac interventions in this high-risk group of stroke patients are warranted.

Septo-optic dysplasia.

Septo-optic dysplasia is a rare disorder characterized by optic nerve hypoplasia; midline developmental defects including agenesis of the septum pellucidum, thinning or absence of the corpus callosum, or both; and deficiencies of pituitary hormones. The majority of cases are sporadic but rare familial cases occur. The clinical manifestations include poor visual function in one or both eyes, developmental delay, seizures, sleep disturbances, and precocious puberty. A life-long multidisciplinary approach is crucial in the management of these patients to optimize their growth and development and to help them lead as normal lives as possible.

[Ecological-faunistical review of fish parasites in the Umbozero Lake (the Kola Peninsula)].

Data on fish infestation by parasites in the Umbozero Lake are given. 90 species of parasites were identified including 16 species of Myxosporea, 2 Suctoria, 18 Peritricha, 12 Monogenea, 13 Cestoda, 18 Trematoda, 5 Nematoda, 2 Acanthocephala, 2 Hirudinea, and 2 species of Crustacea. Character of parasites' distribution in fishes of this lake and ecological peculiarities in the host-parasite system are demonstrated.

[An example of anthropogeneous succession in the ecosystem of the Verkhnetulomsky Water Reservoir (the Tuloma River Basin, the Kola region)].

The destruction of initial biocenoses in the ecosystem of the Verkhnetulomsky Water Reservoir caused deep succession processes. As a result of the loss of the amphipod group in the benthos, replacement of the trophic links in fishes took place in the biocenosis of the reservoir. Benthos feeders changed over to the feeding on zooplankton and, as a result, became the constituent of the predators'diet. The structure of parasitic systems has changed. The parasites using amphipods as intermediate hosts have been and, on the contrary, the abundance of parasites infesting fishes through feeding of the latter on zooplankton has increased. Among the parasites, Triaenophorus crassus Forel became the cause of the appearance of stable triaenophorosis focus.

Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless.

Eclosion, or emergence of adult flies from the pupa, and locomotor activity of adults occur rhythmically in Drosophila melanogaster, with a circadian period of about 24 hours. Here, a clock mutation, timeless (tim), is described that produces arrhythmia for both behaviors. The effects of tim on behavioral rhythms are likely to involve products of the X chromosome-linked clock gene period (per), because tim alters circadian oscillations of per RNA. Genetic mapping places tim on the left arm of the second chromosome between dumpy (dp) and decapentaplegic (dpp).

Use of magnetic resonance angiography to predict long-term outcomes of ischemic stroke patients with concurrent stenoses in Hong Kong.

PURPOSE: To determine the long-term outcome of ischemic stroke patients with concurrent intracranial and extracranial atherosclerosis using magnetic resonance angiography. METHODS: A prospective cohort of patients in Hong Kong with acute ischemic stroke was studied with magnetic resonance angiography of the brain and carotid duplex. All patients were followed up regularly for the development of recurrent stroke, cardiac events, or death. RESULTS: Totally 343 patients with acute ischemic stroke were included, of whom 104 (30%) had concurrent intracranial and extracranial lesions. The follow-up period was up to 76 months (mean 44.5 months). Overall, 55 patients (15.5%) died of any cause and 91 patients (26.5%) suffered a further nonfatal vascular event. The overall 5-year cumulative rates of mortality, restroke and poor outcomes (combined death and further vascular events) were 18, 27 and 37%, respectively. In patients with concurrent lesions, these rates were 31, 41 and 51%, respectively. The corresponding rates were 13, 22 and 31% in patients without concurrent lesions. The risks were highest in the first year after stroke. More deaths (log rank, 16.3; p = 0.0001), restrokes (log rank, 9.71; p = 0.002) and poor outcomes (log rank, 13.87; p = 0.0001) were found among patients with concurrent lesions. The presence of concurrent vascular lesions, advanced age, smoking, hyperlipidemia and previous history of stroke were independent predictors of poor outcomes. CONCLUSIONS: The long-term prognosis of ischemic stroke patients with concurrent atherosclerosis of intracranial and extracranial vessels is poor. They are at high risk of further vascular events or death.

The effects of adjuvant experimental radioimmunotherapy and hyperthermic intraperitoneal chemotherapy on intestinal and abdominal healing after cytoreductive surgery for peritoneal carcinomatosis in the rat.

BACKGROUND: Cytoreductive surgery (CS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) results in limited survival benefit and high morbidity and mortality rates in patients with peritoneal carcinomatosis (PC). Radioimmunotherapy (RIT) after CS of experimental PC has been shown to increase survival and compare favorably to HIPEC. The effects of RIT and HIPEC on wound healing after CS need to be determined. METHODS: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. Animals were subjected to CS and anastomotic construction only or followed by RIT or HIPEC. RIT consisted of 74 MBq (177)lutetium-labeled anti-CC531 antibody MG1. HIPEC was performed by a closed abdominal perfusion technique using mitomycin-C during 60 minutes. Anastomotic and abdominal wall strength measurements were performed 3 and 5 days after surgery. RESULTS: At day 5, bursting pressure in ileum and colon anastomoses in the CS + HIPEC group, but not in the CS + RIT group, was lower (P < .01) than in the CS group. In the CS group, the colonic bursting site was more often outside the true anastomotic area (8 of 12 animals) than in the CS + HIPEC (1 of 12) and CS + RIT (5 of 12) groups. Abdominal wall strength in the CS + HIPEC group was significantly (P < .01) lower, at both measuring points, than that in both the CS group and the CS + RIT group. There was no difference between the latter. CONCLUSION: As adjuvant to CS, HIPEC showed a decrease in anastomotic and abdominal wall wound strength in a model of PC of CRC, whereas RIT did not.

Vigabatrin-induced visual dysfunction in Chinese patients with refractory epilepsy.

PURPOSE: Bilateral visual field constriction has been reported following the use of the antiepileptic drug (AED) vigabatrin. The incidence of retinal toxicity is variable and there are limited data in Asian populations. The authors report the results of ophthalmologic examination in Chinese patients taking this drug. METHODS: The authors identified two groups of patients with refractory epilepsy: one group on vigabatrin and another cohort of patients taking other AEDs. The authors recorded the medical history and performed visual acuity testing, intraocular pressure measurement, slit lamp biomicroscopy, and conventional automated perimetry with Humphrey Visual Field Analyzer II in all patients. RESULTS: Eighteen patients--8 men and 10 women--with a mean age of 23.8 years who were taking vigabatrin were reviewed. Length of treatment with this drug ranged from 13 months to 5 years and the mean daily dosage was 1581 mg. None of the patients in either group had a history of coexisting optic nerve diseases or other neurotoxic drug use. Twenty of 36 (55.6%) eyes of the vigabatrin users showed significant bilateral visual field defects with 80% showing a concentric pattern, compared with none in the control group. CONCLUSIONS: The authors confirmed a high prevalence of visual field constriction associated with vigabatrin in Chinese patients. The use of alternative novel techniques such as measurement of the retinal nerve fibre layer thickness and perimetry may detect early retinal damage and result in even higher incidences. Visual field monitoring is recommended in patients who continue to take this drug.

[Long-term changes in the epizootic of juvenile salmon (Salmo salar L.) in the Keret River (White Sea basin) depending on the invasion of Gyrodactylus salaris Malmberg, 1957].

Results of long-term investigations on the population dynamics of juvenile Atlantic salmon (Salmo salar L.) in the Keret' river (White Sea drainage basin) depending on the invading of Gyrodactylus salaris (Malmberg, 1957) and mass infestation of salmon with this parasite are presented. Gyrodactylus salaris was for the first time recorded in the Keret' river in 1992. During the period lesser than five years the parasite spread along the river. The rise in the infestation of salmon parr with G. salaris caused death of the fish host. As the abundance of juveniles decreased, adult salmon stocks dropped more than 25 times. It was shown, that after the decreasing in number of salmon juveniles following acute epizootic, infestation parameters dropped, and in some years G. salaris was not even found at all.