An old unknown: 40 years of crayfish plague monitoring in Switzerland, the water tower of Europe.

The oomycete Aphanomyces astaci is the causative agent of crayfish plague, a disease threatening susceptible freshwater crayfish species in Europe. To detect its spatiotemporal occurrence in Switzerland, we reviewed (1) the literature regarding occurrence of crayfish plague and North American crayfish carrier species and (2) the necropsy report archive of the Institute for Fish and Wildlife Health (FIWI) from 1968 to 2020. In the past, crayfish plague was diagnosed through several methods: conventional PCR, culture, and histology. When available, we re-evaluated archived Bouin's or formalin-fixed, paraffin-embedded samples collected during necropsies (1991-2020) with a recently published quantitative PCR. Literature research revealed putative reports of crayfish plague in Switzerland between the 1870s and 1910s and the first occurrence of three North American crayfish species between the late 1970s and 1990s. Finally, 54 (28.1%) cases were classified as positive and 9 (4.7%) cases as suspicious. The total number of positive cases increased by 14 (14.7%) after re-evaluation of samples. The earliest diagnosis of crayfish plague was performed in 1980 and the earliest biomolecular confirmation of A. astaci DNA dated 1991. Between 1980-1990, 1991-2000 and 2001-2010 crayfish plague spread from one to two and finally three catchment basins, respectively. Similar to other European countries, crayfish plague has occurred in Switzerland in two waves: the first at the end of the 19th and the second at the end of the 20th century in association with the first occurrence of North American crayfish species. The spread from one catchment basin to another suggests a human-mediated pathogen dispersal.

The developmental course of adolescent paranoia: a longitudinal analysis of the interacting role of mistrust and general psychopathology.

Paranoia is the erroneous idea that people are targeting you for harm, and the cognitive model suggests that symptoms increase with emotional and relational distress. A factor potentially associated with paranoia is mistrust, a milder form of suspiciousness. This study investigated the longitudinal course of non-clinical paranoia in a sample of 739 students (age range 10-12 at baseline assessment, 12-14 at second assessment) using data from the Social Mistrust Scale (SMS) and the paranoia subscale of the Specific Psychotic Experiences Questionnaire (SPEQ). Prevalence of mistrustful and high paranoia children was 14.6 and 15% respectively. Independently, baseline internalizing symptoms (b = 0.241, p < 0.001) and mistrust (b = 0.240, p < 0.001) longitudinally predict paranoia after controlling for confounders. The interaction of mistrust and internalizing symptoms at T1 increases the possibility of the onset of paranoia at T2. Therefore, the effect of mistrust on paranoia is more marked when internalizing symptoms are higher. Our results confirm the role of mistrust as a factor involved in the developmental trajectory of paranoia in adolescence, enhanced by the presence of internalizing symptoms. The implications of these results are both theoretical and clinical, as they add developmental information to the cognitive model of paranoia and suggests the assessment and clinical management of mistrust and internalizing symptoms in youth may be useful with the aim of reducing the risk of psychotic experiences.

Assessing Callous-Unemotional Traits Across Early Adolescence: Further Evaluation of Short Versions.

Literature on the Inventory of Callous-Unemotional (ICU) traits has suggested different versions of the instrument for assessing these traits during development. However, consensus on the instrument version and the best factorial solution remains a matter of debate, with only a few studies having validated ICU versions from a longitudinal perspective. The current study aims to contribute to the literature by comparing ICU models in a longitudinal sample of early adolescents (N = 739; 70.6% of eligible subjects, 371 females and 368 males, in the 6th grade at baseline assessment and in the 8th grade at the second assessment). We tested the validity of various versions of the ICU scales and their respective dimensions by conducting a series of confirmatory factor analyses to verify the factor structure, alongside assessments of internal consistency. For the best-fitting structure, we then analyzed gender and longitudinal invariance in addition to construct and predictive validity, using internalizing and externalizing criteria as well as prosocial behavior. From the comparative analysis, it emerged that the abbreviated 11-item ICU scale version displayed overall better data fit than the full 24-item version. Moreover, its confirmed gender invariance underscores its applicability across genders within the studied age group. With regard to longitudinal invariance, our findings advise caution when comparing ICU scores across early adolescence. Practical implications are discussed.

The association between social isolation, loneliness and psychological problems in young adults: A study during the acute phase of COVID-19 in Italy.

During the COVID-19 pandemic, governments had to impose social isolation measures to safeguard the citizens' health. However, this could have affected psychological problems. The aim of the present study was to investigate the psychological effects associated with social and emotional isolation during the acute phase of the COVID-19 in Italy. To this purpose, the degree of social isolation and loneliness and the presence of psychological problems (externalising and internalising) were investigated online in a sample of 395 young adults (18-30 years; 57% women). Results confirmed the relevant association between social isolation, loneliness and psychological problems, in both internalising and externalising dimensions. Particularly, loneliness showed the strongest association. Moreover, consistently with surveys conducted during the COVID-19-era, data highlighted that men were more vulnerable to social isolation and loneliness than women. These results underline the need for adequate interpersonal support during moments of isolation to prevent negative effects on psychological problems.

LISTERIA MONOCYTOGENES INFECTION IN FREE-RANGING RED FOXES (VULPES VULPES) AND EURASIAN LYNX (LYNX LYNX) IN SWITZERLAND.

Listeria monocytogenes is an ubiquitous environmental saprophytic bacterium causing listeriosis in domestic animals, humans, and occasionally wildlife. In animals, this foodborne zoonotic disease mainly occurs in ruminants and it is rare in carnivores. Seven red foxes (Vulpes vulpes) and one Eurasian lynx (Lynx lynx) were diagnosed with listeriosis between 2010 and 2021 at the Institute for Fish and Wildlife Health, Bern, Switzerland. Necropsy and histopathology revealed meningitis (six of seven red foxes), hepatitis (six of seven red foxes), pneumonia (five of seven red foxes), splenitis (two of seven red foxes) and splenomegaly (the Eurasian lynx, two of seven red foxes). Listeria monocytogenes was isolated from either lung, spleen, liver, or kidney of all animals. Serotyping detected L. monocytogenes serotype 1/2a in five red foxes and the Eurasian lynx and serotype 4b in two red foxes. Six red foxes were positive for canine distemper virus (CDV) by polymerase chain reaction, whereas the Eurasian lynx and one red fox were negative. One red fox that was positive for CDV and listeriosis was also diagnosed with salmonellosis. The identified L. monocytogenes serotypes are among the three most frequently isolated serotypes (1/2a, 1/2b, and 4b) from food or the food production environment and those that cause most listeriosis cases in humans and animals. Coinfection with CDV in six red foxes questions the role of CDV as potential predisposing factor for septicemic listeriosis. The detection of listeriosis in the regionally endangered Eurasian lynx and in carnivores highly abundant in urban settings, such as red foxes, reinforces the importance of wildlife health surveillance in a One Health context and adds the Eurasian lynx to the list of carnivores susceptible to the disease. Further investigations are required to assess the prevalence and epidemiology of L. monocytogenes in free-ranging carnivores and its interaction with CDV.

Stereodivergent synthesis with a programmable molecular machine.

It has been convincingly argued that molecular machines that manipulate individual atoms, or highly reactive clusters of atoms, with Ångström precision are unlikely to be realized. However, biological molecular machines routinely position rather less reactive substrates in order to direct chemical reaction sequences, from sequence-specific synthesis by the ribosome to polyketide synthases, where tethered molecules are passed from active site to active site in multi-enzyme complexes. Artificial molecular machines have been developed for tasks that include sequence-specific oligomer synthesis and the switching of product chirality, a photo-responsive host molecule has been described that is able to mechanically twist a bound molecular guest, and molecular fragments have been selectively transported in either direction between sites on a molecular platform through a ratchet mechanism. Here we detail an artificial molecular machine that moves a substrate between different activating sites to achieve different product outcomes from chemical synthesis. This molecular robot can be programmed to stereoselectively produce, in a sequential one-pot operation, an excess of any one of four possible diastereoisomers from the addition of a thiol and an alkene to an α,ß-unsaturated aldehyde in a tandem reaction process. The stereodivergent synthesis includes diastereoisomers that cannot be selectively synthesized through conventional iminium-enamine organocatalysis. We anticipate that future generations of programmable molecular machines may have significant roles in chemical synthesis and molecular manufacturing.

Amphibian regeneration and mammalian cancer: Similarities and contrasts from an evolutionary biology perspective: Comparing the regenerative potential of mammalian embryos and urodeles to develop effective strategies against human cancer.

Here we review and discuss the link between regeneration capacity and tumor suppression comparing mammals (embryos versus adults) with highly regenerative vertebrates. Similar to mammal embryo morphogenesis, in amphibians (essentially newts and salamanders) the reparative process relies on a precise molecular and cellular machinery capable of sensing abnormal signals and actively reprograming or eliminating them. As the embryo's evil twin, tumor also retains common functional attributes. The immune system plays a pivotal role in maintaining a physiological balance to provide surveillance against tumor initiation or to support its initiation and progression. We speculate that susceptibility to cancer development in adult mammals may be determined by the loss of an advanced regenerative capability during evolution and believe that gaining mechanistic insights into how regenerative capacity linked to tumor suppression is postnatally lost in mammals might illuminate an as yet unrecognized route to cancer treatment.

Comparison of exoskeleton microbial communities of co-occurring native and invasive crayfish species.

Host-associated microbial communities are an important determinant of individual fitness and have recently been highlighted as one of the factors influencing the success of invasive species. Invasive hosts introduce their microbes into the new environment, and then both the host and its associated microbes enter into a series of interactions with the native macroscopic and microscopic biota. As these processes are largely unexplored, we aimed to compare the exoskeletal microbial communities of co-occurring and phylogenetically related crayfish: the native narrow-clawed crayfish Pontastacus leptodactylus and the invasive signal crayfish Pacifastacus leniusculus from the recently invaded Korana River, Croatia. The results of high-throughput 16S rRNA sequencing showed that the exoskeletal microbiome of both species is very diverse, significantly influenced by the local environment and dominated by low abundance bacterial families from the phylum Proteobacteria. Furthermore, the exoskeletal microbiomes of the crayfish species differed significantly in the composition and abundance of Amplicon Sequence Variants (ASVs), suggesting that they are to some extent shaped by species-specific intrinsic factors, despite sharing a common habitat. However, over 95% of the bacterial genera associated with the exoskeleton were detected in the exoskeleton samples of both native and invasive crayfish. We paid particular attention to two known crayfish pathogens, Aphanomyces astaci and Saprolegnia parasitica, and find that both species carry low amounts of both pathogens. On the side, we find that a non-standard ddPCR protocol outperforms standard qPCR test for A. astaci under low concentration conditions. Taken together, our results indicate the possibility of bidirectional mixing and homogenisation of exoskeleton microbiome. As such, they can serve as a baseline in future detangling of the processes that act together to shape the microbiomes of co-occuring native and invasive congeners during biological invasions.

Detection of novel RNA viruses in wild noble crayfish (Astacus astacus): A virome analysis in Swiss water bodies.

European native crayfish populations are undergoing a strong decline due to environmental factors and the introduction of highly competitive non-native species. Pathogens are an additional threat to native crayfish. However, aside from the crayfish plague, other infectious diseases are still widely unknown. This study aimed to investigate viruses present in seven populations of wild noble crayfish (Astacus astacus) in Switzerland, through high-throughput sequencing. Sequence analysis revealed the presence of 11 novel RNA viruses (one bunya-like, four hepe-like, two dicistro-like, three picorna-like, and one permutotetra-like) in the samples. The discovery of a novel bunya-like virus in noble crayfish without associated mortality or macroscopical alterations is of particular interest since it is closely related to the bunya-like brown spot virus, a virus described in 2019 from diseased native white-clawed crayfish (Austropotamobius pallipes) during a mass mortality event in France. It seems that these two closely related viruses have very different impacts on their respective hosts, raising the need for further investigations on virulence factors and host susceptibility towards these viruses. This study provides a basis for future investigations, permitting to gradually fill the knowledge gap in crayfish viral diseases.

Ophiodimyces ophiodiicola, Etiologic Agent of Snake Fungal Disease, in Europe since Late 1950s.

The fungus Ophiodimyces ophiodiicola is the etiologic agent of snake fungal disease. Recent findings date US occurrence at least as far back as 1945. We analyzed 22 free-ranging snakes with gross lesions consistent with snake fungal disease from museum collections from Europe. We found 5 positive samples, the oldest collected in 1959.

Weight and body mass index increase in children and adolescents exposed to antipsychotic drugs in non-interventional settings: a meta-analysis and meta-regression.

Antipsychotics increase weight, BMI and waist size, particularly in pediatric patients. Switching antipsychotics is common practice, thus defining the risk for each antipsychotic in real-life settings can be important for clinical guidance. We conducted a meta-analysis on antipsychotic-related changes in body measures in pediatric observational studies. Of 934 publications found on PubMed, we analyzed 38, including nine treatment arms: no treatment, mixed antipsychotic treatment, first-generation antipsychotics, aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone. Changes in weight, BMI, BMI-Z and waist size were meta-analyzed according to the duration of clinical observations: 6, 12, > 12 months. Meta-regressions probed influencing factors. Weight in Kg was increased at 6, 12, > 12 months by olanzapine [+ 10.91, + 10.7, data not available (n/a)], mixed antipsychotic treatment (n/a, + 9.42, + 12.59), quetiapine (+ 5.84, n/a, n/a) and risperidone (+ 4.47, + 6.01, + 9.51) and without treatment (n/a, + 2.3, n/a). BMI was increased at 6, 12, > 12 months by olanzapine (+ 3.47, + 3.42, n/a), clozapine (n/a, + 3, n/a) mixed antipsychotic treatment (+ 3.37, + 2.95, + 3.32), risperidone (+ 2, + 2.13, + 2.16), quetiapine (+ 1.5, + 1.82, n/a), aripiprazole (n/a, + 1.7, + 2.1) and without treatment (n/a, + 0.75, n/a). BMI-Z was increased at 6, 12, > 12 months by olanzapine (+ 0.94, + 0.98, + 0.89), clozapine (n/a, + 0.8, n/a), risperidone (+ 0.62, + 0.61, + 0.48), quetiapine (+ 0.57, + 0.54, n/a), mixed antipsychotic treatment (+ 0.51, + 0.94, + 0.44), without treatment (n/a, + 0.37, n/a) and aripiprazole (no gain, + 0.31, n/a). Waist size in cm was increased at 6, 12 months by risperidone (+ 8.8, + 11.5), mixed antipsychotics treatment (+ 9.1, + 10.2) and quetiapine (+ 6.9, + 9.1). Overall, olanzapine and clozapine displayed maximum risk, followed by risperidone, quetiapine and aripiprazole (more risky at longer terms); ziprasidone was associated with no gains. No time-based trends emerged, suggesting a drug-specific risk magnitude. Meta-regressions evidenced variable roles for persistence in therapy and follow-up length, increased risk for drug-naïve patients, and a ceiling effect determined by higher baseline BMI/BMI-Z values.

Detection of Metabolite-Protein Interactions in Complex Biological Samples by High-Resolution Relaxometry: Toward Interactomics by NMR.

Metabolomics, the systematic investigation of metabolites in biological fluids, cells, or tissues, reveals essential information about metabolism and diseases. Metabolites have functional roles in a myriad of biological processes, as substrates and products of enzymatic reactions but also as cofactors and regulators of large numbers of biochemical mechanisms. These functions involve interactions of metabolites with macromolecules. Yet, methods to systematically investigate these interactions are still scarce to date. In particular, there is a need for techniques suited to identify and characterize weak metabolite-macromolecule interactions directly in complex media such as biological fluids. Here, we introduce a method to investigate weak interactions between metabolites and macromolecules in biological fluids. Our approach is based on high-resolution NMR relaxometry and does not require any invasive procedure or separation step. We show that we can detect interactions between small and large molecules in human blood serum and quantify the size of the complex. Our work opens the way for investigations of metabolite (or other small molecules)-protein interactions in biological fluids for interactomics or pharmaceutical applications.

Association between the glyco-metabolic adverse effects of antipsychotic drugs and their chemical and pharmacological profile: a network meta-analysis and regression.

BACKGROUND: Glyco-metabolic deteriorations are the most limiting adverse reactions to antipsychotics in the long term. They have been incompletely investigated and the properties of antipsychotics that determine their magnitude are not clarified.To rank antipsychotics by the magnitude of glyco-metabolic alterations and to associate it to their pharmacological and chemical properties, we conducted a network meta-analysis. METHODS: We searched PubMed, Embase, and Psycinfo on 10 September 2020. We selected studies containing the endpoint-baseline difference or the distinct values of at least one outcome among glucose, HbA1c, insulin, HOMA-IR, triglycerides, total/HDL/LDL cholesterols. Of 2094 articles, 46 were included in network meta-analysis. Study quality was assessed by the RoB 2 and ROBINS-I tools. Mean differences (MD) were obtained by random-effects network meta-analysis; relations between MD and antipsychotic properties were analyzed by linear regressions. Antipsychotic properties investigated were acidic and basic pKa, polar surface area, polarizability, and occupancies of D2, H1, M1, M3, α1A, α2A, 5-HT1A, 5-HT2A, 5-HT2C receptors. RESULTS: We meta-analyzed 46 studies (11 464 patients); on average, studies lasted 15.47 weeks, patients had between 17.68 and 61.06 years of mean age and 61.64% were males. Olanzapine and clozapine associated with greater deteriorations, aripiprazole and ziprasidone with smaller deteriorations. Higher polarizability and 5-HT1A receptor occupancy were associated with smaller deteriorations, H1, M1, and M3 receptor occupancies with larger deteriorations. CONCLUSIONS: Drug rankings may guide antipsychotic switching toward metabolically safer drugs. Mechanistic insights may suggest improvements for combination therapies and drug development. More data are required regarding newer antipsychotics.

First description of peritoneal and pleural metacestodosis caused by Mesocestoides vogae in a European wild cat (Felis silvestris silvestris).

Tapeworms of the genus Mesocestoides (Cestoda: Cyclophyllidea: Mesocestoididae) are still enigmatic to scientists, due to their high morphological variability, low host specificity, and unknown details of their life cycle. They are found worldwide, with carnivorous mammals as the main definitive hosts, and the disease is potentially zoonotic. After ingestion by a definitive host, the tetrathyridium can occasionally migrate through the intestinal wall and reach the peritoneal cavity or abdominal organs causing peritoneal metacestodosis. Here, we report on a case of metacestodosis of a European wild cat (Felis silvestris silvestris) found dead in Croatia. At necropsy, a large number of white, rice-like structures were found free in the abdominal and thoracic cavities, as well as along the serous surfaces and in the lungs. DNA isolated from the nodules was genotyped and based on a 320-base pair long 12S fragment classified as Mesocestoides vogae. Although post-mortem changes were advanced, severe emaciation due to the severe parasitic infection and gastrointestinal bleeding was diagnosed as the likely cause of death. Intestinal cestodosis was previously reported in wild cats, but according to our knowledge, this is the first description of peritoneal and pleural metacestodosis caused by M. vogae tetrathyridia (metacestodes) in any wild carnivore species.

Ex vivo study of vagal branches at risk for iatrogenic injury during laryngoplasty in horses.

OBJECTIVE: To localize vagal branches within the surgical field of laryngoplasty and identify potentially hazardous surgical steps. STUDY DESIGN: Observational cadaveric study. SAMPLE POPULATION: Five equine head-neck specimens and four entire equine cadavers. METHODS: Dissection of the pharyngeal region from a surgical perspective. Neuronal structures were considered at risk if touched or if the distance to instruments was less than 5 mm. RESULTS: The branches of the pharyngeal plexus (PP) supplying the cricopharyngeal muscle (PPcr), the thyropharyngeal muscle (PPth), and the esophagus (PPes) were identified in the surgical field in nine of nine, five of nine, and one of nine specimens, respectively. The internal branch of the cranial laryngeal nerve (ibCLN) was identified within the carotid sheath in six of nine specimens. The external branch of the cranial laryngeal nerve (ebCLN) was identified close to the septum of the caudal constrictors in nine of nine specimens. The blade of the tissue retractor compressed the ibCLN in six of six, the ebCLN in four of six, the PPcr in six of six, the PPth in two of three, and the PPes in two of two specimens in which the respective nerves were identified after further dissection. Surgical exploration of the dorsolateral aspect of the pharynx and the incision of the septum of the caudal constrictors harmed the ebCLN in nine of nine, PPcr in seven of nine, and PPth in four of eight specimens. CONCLUSION: Several vagal branches were located in the surgical field and must be considered at risk because of their location. CLINICAL SIGNIFICANCE: Use of the tissue retractor, dissection over the pharynx, and dissection of the septum of the caudal constrictors involve a risk to damage vagal branches.

Coping Power Universal for middle school students: The first efficacy study.

INTRODUCTION: The present study examined the efficacy of the universal prevention version of the Coping Power Program in reducing behavioral and emotional problems and in promoting prosocial behaviors in middle-school classrooms. METHODS: The study used a randomized control study design; and the sample included 839 middle-school Italian youths (411 males), attending 40 middle-school classrooms. The students were in seventh or eighth grade, and they had an average age of 13.24 years (SD = .65; range 12-14 years). Ninety students were Africans, the rest were Caucasian. Teachers and parents completed the Strengths and Difficulties Questionnaire, before and after intervention. We used the 24-session universal prevention adaptation of Coping Power, which aims to improve children's emotional regulation and social problem-solving skills. RESULTS: Linear mixed models and effect sizes indicated that behaviors improved as a result of the Coping Power intervention. Specifically, the program was effective in reducing internalizing problems and increasing prosocial behaviors. CONCLUSIONS: The Coping Power Universal effectively adapts an existing evidence-based program, and is believed to be a useful strategy also to improve social emotional skills in middle-school students.

A glance into psychiatric comorbidity in adolescents with anorexia nervosa.

BACKGROUND: Eating disorders display several psychiatric comorbidities. The aim of this study was to describe these comorbidities in a group of adolescent patients with anorexia nervosa or OSFED (Other Specified Feedind or Eating Disorder). We have evaluated the comorbidity both with a clinical interview (categorical comorbidities) and with a self-report interview (dimensional comorbidities) in order to compare the two profiles. METHODS: The study was carried out at the Division of Child and Adolescent Psychiatry (eating disorder service for developmental age) of the Luigi Vanvitelli University of Campania (ex Second University of Naples). Data were collected retrospectively from chart review, routinely gathered during the clinical assessment. RESULTS: Seventy-two subjects constituted the sample, 62 (86.1%) were female and 10 (13.9%) male. The most frequent categorical comorbidities were social anxiety disorder (SS: 38; 52.8%), Depression disorder (SS: 30; 41.7%) and generalized anxiety disorder (SS: 14; 19.4%). The mean scores at dimensional questionnaires were 15.5 (SD: 10.7) for the depression (Children Depression Inventory) and 34.8 (SD: 28.3) for social anxiety (Liebowitz Social Anxiety Scale). CONCLUSIONS: Data analysis showed that social anxiety and depression were the most common categorical comorbidities in young patients with eating disorders. However, comparing the data from the clinical interview with those of the self-interviews revealed that patients well recognize social anxiety symptoms, but tend to deny depressive ones.

Sarcoptic Mange of Fox Origin in Multiple Farm Animals and Scabies in Humans, Switzerland, 2018.

Fox-derived Sarcoptes scabiei mites caused an outbreak of mange on a farm in Switzerland in 2018. Pruritic skin lesions suggestive of S. scabiei mite infestation developed in 4 humans who had direct contact with affected farm animals but not foxes. Sarcoptic mange is continuously spreading; such outbreaks affecting humans could start occurring more frequently.

Nanotechnology and Immunotherapy in Ovarian Cancer: Tracing New Landscapes.

Ovarian cancer (OC) is the seventh most common cancer in women worldwide. Standard therapeutic treatments involve debulking surgery combined with platinum-based chemotherapies. Of the patients with advanced-stage cancer who initially respond to current treatments, 50%-75% relapse. Immunotherapy-based approaches aimed at boosting antitumor immunity have recently emerged as promising tools to challenge tumor progression. Treatments with inhibitors of immune checkpoint molecules have shown impressive results in other types of tumors. However, only 15% of checkpoint inhibitors evaluated have proven successful in OC due to the immunosuppressive environment of the tumor and the transport barriers. This limits the efficacy of the existing immunotherapies. Nanotechnology-based delivery systems hold the potential to overcome such limitations. Various nanoformulations including polymeric, liposomes, and lipid-polymer hybrid nanoparticles have already been proposed to improve the biodistribution and targeting capabilities of drugs against tumor-associated immune cells, including dendritic cells and macrophages. In this review, we examine the impact of immunotherapeutic approaches that are currently under consideration for the treatment of OC. In this review, we also provide a comprehensive analysis of the existing nanoparticle-based synthetic strategies and their limitations and advantages over standard treatments. Furthermore, we discuss how the strength of the combination of nanotechnology with immunotherapy may help to overcome the current therapeutic limitations associated with their individual application and unravel a new paradigm in the treatment of this malignancy.

Liquid crystal delivery of ciprofloxacin to treat infections of the female reproductive tract.

Infections of the female reproductive tract are a major cause of morbidity and mortality in humans, requiring significant investment to sustain treatment and representing a major challenge to health. The increasing prevalence of bacterial resistance, and an almost complete absence of new antibiotic therapies for the past five decades, mean there is a desperate need for novel approaches to the treatment of bacterial infections. Within the present study, we demonstrate the effective ex vivo treatment of bacterial infection of the female reproductive tract using a controlled-release, liquid crystal-based platform. Liquid crystal encapsulation of ciprofloxacin significantly enhanced its bactericidal efficacy and reduced cell toxicity. Liquid crystal structures are low-cost, simple to manufacture and provide a sustained-release profile of encapsulated ciprofloxacin. Treatment of Escherichia coli infected reproductive tract epithelial cells and whole organ cultures with liquid crystal encapsulated ciprofloxacin proved to be an effective strategy for reducing bacterial load and reproductive tract inflammatory responses to infection. These data suggest that such an approach could provide an efficacious treatment modality for enhancing the effectiveness of current antibiotic therapies.