Sepsis exacerbates Alzheimer's disease pathophysiology, modulates the gut microbiome, increases neuroinflammation and amyloid burden.

While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task was performed 30 and 120 days after the surgery, and sepsis accelerated the cognitive decline in APP/PS1 mice at both time points. At 120 days, the insoluble Aß increased in the sepsis group, and sepsis modulated the cytokines/chemokines, decreasing the cytokines associated with brain homeostasis IL-10 and IL-13 and increasing the eotaxin known to influence cognitive function. At 120 days, we found an increased density of IBA-1-positive microglia in the vicinity of Aß dense-core plaques, compared with the control group confirming the predictable clustering of reactive glia around dense-core plaques within 15 µm near Aß deposits in the brain. In the gut, sepsis negatively modulated the α- and ß-diversity indices evaluated by 16S rRNA sequencing, decreased the levels of SCFAs, and significantly affected ileum and colon morphology in CLP mice. Our data suggest that sepsis-induced peripheral infection accelerates cognitive decline and AD pathology in the AD mouse model.

Neurochemical effects of sepsis on the brain.

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host immune response to eliminate an infection. After the host immune response is activated, a complex, dynamic, and time-dependent process is triggered. This process promotes the production of inflammatory mediators, including acute-phase proteins, complement system proteins, cytokines, chemokines, and antimicrobial peptides, which are required to initiate an inflammatory environment for eliminating the invading pathogen. The physiological response of this sepsis-induced systemic inflammation can affect blood-brain barrier (BBB) function; subsequently, endothelial cells produce inflammatory mediators, including cytokines, chemokines, and matrix metalloproteinases (MMPs) that degrade tight junction (TJ) proteins and decrease BBB function. The resulting BBB permeability allows peripheral immune cells from the bloodstream to enter the brain, which then release a range of inflammatory mediators and activate glial cells. The activated microglia and astrocytes release reactive oxygen species (ROS), cytokines, chemokines, and neurochemicals, initiate mitochondrial dysfunction and neuronal damage, and exacerbate the inflammatory milieu in the brain. These changes trigger sepsis-associated encephalopathy (SAE), which has the potential to increase cognitive deterioration and susceptibility to cognitive decline later in life.

Pre-treatment and continuous administration of simvastatin during sepsis improve metabolic parameters and prevent CNS injuries in survivor rats.

Sepsis causes overproduction of inflammatory cytokines, organ dysfunction, and cognitive impairment in survivors. In addition to inflammation, metabolic changes occur according to the stage and severity of the disease. Understanding the role and place of metabolic disturbances in the pathophysiology of sepsis is essential to evaluate the framework of septic patients, predict the syndrome progress, and define the treatment strategies. We investigated the effect of simvastatin on the disease time course and on metabolic alterations, especially with respect to their possible consequences in the CNS of surviving rats. The animals of this study were weighed daily and followed for 10 days to determine the survival rate. In the first experiment, control or cecal ligation and puncture (CLP)-animals were randomized in 24 h, 48 h, and 10 days after septic induction, for bacterial load determination and quantification of cytokines. In the second experiment, control or CLP-animals were treated or not with simvastatin and randomized in the same three time points for cytokines quantification and assessment of their body metabolism and locomotor activity (at 48 h and 10 days), as well as the evaluation of cytoarchitecture and astrogliosis (at 10 days). The CLP-rats treated with simvastatin showed a reduction in plasma cytokines and improvement in metabolic parameters and locomotor activity, followed by minor alterations compatible with apoptosis and astrogliosis in the hippocampus and prefrontal cortex. These results suggest that the anti-inflammatory effect of simvastatin plays a crucial role in restoring energy production, maintaining a hypermetabolic state necessary for the recovery and survival of these CLP-rats.

Corticosterone and Adrenocorticotrophic Hormone Secretion Is Recovered after Immune Challenge or Acute Restraint Stress in Sepsis Survivor Animals.

BACKGROUND: Clinical and experimental studies report a dysregulation of hypothalamus-pituitary-adrenal (HPA) axis during sepsis that causes impairment in hormone secretion in the late phase contributing for the pathophysiology of the disease. However, it is unclear whether this alteration persists even after the disease remission. METHODS: We evaluated the effect of an immune challenge or restraint stress on the hormone secretion of HPA axis in sepsis survivor rats. Sepsis was induced by cecal ligation-puncture (CLP) surgery. Naive or animals that survive 5 or 10 days after CLP were submitted to lipopolysaccharide (LPS) injection or restraint stress. After 60 min, blood was collected for plasma nitrate, cytokines, adrenocorticotropic hormone (ACTH), and corticosterone (CORT) and brain for synaptophysin and hypothalamic cytokines. RESULTS: Five days survivor animals showed increased plasma nitrate (p < 0.001) and interleukin (IL)-1ß levels (p < 0.05) that were abolished in the 10 days survivors. In the hypothalamus of both survivors, the reverse was seen with IL-6 increased (p < 0.01), while IL-1ß did not show any alteration. Synaptophysin expression was reduced in both survivors and did not change after any stimuli. Only the LPS administration increased plasma and/or inflammatory mediators levels in both groups (survivors and naive) being apparently lower in the survivors. There was no difference in the increased secretion pattern of ACTH and CORT observed in the naive and sepsis survivor animals submitted to immune challenge or restraint stress. CONCLUSION: We conclude that the HPA axis is already recovered soon after 5 days of sepsis induction responding with normal secretion of ACTH and CORT when required.

Budget impact analysis of cervical cancer screening in Portugal: comparison of cytology and primary HPV screening strategies.

BACKGROUND: Primary Human Papilloma Virus (HPV) testing is the currently recommended cervical cancer (CxCa) screening strategy by the Portuguese Society of Gynecology (SPG) clinical consensus. However, primary HPV testing has not yet been adopted by the Portuguese organized screening programs. This modelling study compares clinical benefits and costs of replacing the current practice, namely cytology with ASCUS HPV triage, with 2 comparative strategies: 1) HPV (pooled) test with cytology triage, or 2) HPV test with 16/18 genotyping and cytology triage, in organized CxCa screenings in Portugal. METHODS: A budget impact model compares screening performance, clinical outcomes and budget impact of the 3 screening strategies. A hypothetical cohort of 2,078,039 Portuguese women aged 25-64 years old women is followed for two screening cycles. Screening intervals are 3 years for cytology and 5 years for the HPV strategies. Model inputs include epidemiological, test performance and medical cost data. Clinical impacts are assessed with the numbers of CIN2-3 and CxCa detected. Annual costs, budget impact and cost of detecting one CIN2+ were calculated from a public healthcare payer's perspective. RESULTS: HPV testing with HPV16/18 genotyping and cytology triage (comparator 2) shows the best clinical outcomes at the same cost as comparator 1 and is the most cost-effective CxCa screening strategy in the Portuguese context. Compared to screening with cytology, it would reduce annual CxCa incidence from 9.3 to 5.3 per 100,000, and CxCa mortality from 2.7 to 1.1 per 100,000. Further, it generates substantial cost savings by reducing the annual costs by €9.16 million (- 24%). The cost of detecting CIN2+ decreases from the current €15,845 to €12,795. On the other hand, HPV (pooled) test with cytology triage (comparator 1) reduces annual incidence of CxCa to 6.9 per 100,000 and CxCa mortality to 1.6 per 100,000, with a cost of €13,227 per CIN2+ detected with annual savings of €9.36 million (- 24%). The savings are mainly caused by increasing the length of routine screening intervals from three to five years. CONCLUSION: The results support current clinical recommendations to replace cytology with HPV with 16/18 genotyping with cytology triage as screening algorithm.

HSP-Target of Therapeutic Agents in Sepsis Treatment.

Sepsis is a syndrome characterized by a dysregulated inflammatory response, cellular stress, and organ injury. Sepsis is the main cause of death in intensive care units worldwide, creating need for research and new therapeutic strategies. Heat shock protein (HSP) analyses have recently been developed in the context of sepsis. HSPs have a cytoprotection role in stress conditions, signal to immune cells, and activate the inflammatory response. Hence, HSP analyses have become an important focus in sepsis research, including the investigation of HSPs targeted by therapeutic agents used in sepsis treatment. Many therapeutic agents have been tested, and their HSP modulation showed promising results. Nonetheless, the heterogeneity in experimental designs and the diversity in therapeutic agents used make it difficult to understand their efficacy in sepsis treatment. Therefore, future investigations should include the analysis of parameters related to the early and late immune response in sepsis, HSP localization (intra or extracellular), and time to the onset of treatment after sepsis. They also should consider the differences in experimental sepsis models. In this review, we present the main results of studies on therapeutic agents in targeting HSPs in sepsis treatment. We also discuss limitations and possibilities for future investigations regarding HSP modulators.

Impairment of osmotic challenge-induced neurohypophyseal hormones secretion in sepsis survivor rats.

BACKGROUND/PURPOSE: Recent studies have reported that sepsis survivors show impaired central nervous system functions. The osmoregulation in this post-sepsis condition has not been well investigated. In the present study, we evaluated the secretion of neurohypophyseal hormones, arginine vasopressin (AVP) and oxytocin (OT), and water intake induced by osmotic challenge in survivor rats. METHODS: Wistar rats were submitted to sepsis by cecal ligation and puncture (CLP). Five days after CLP surgery, the survivor and naive animals were stimulated with an osmotic challenge consisting of hypertonic saline administration. Thirty minutes later, blood and brain were collected for determination of osmolality, nitrite, interleukin (IL)-1ß, IL-6, AVP and OT levels and c-fos expression analysis of hypothalamic supraoptic nuclei (SON), respectively. In another set of sepsis survivor animals, water intake was measured for 240 min after the osmotic stimulus. RESULTS: High levels of nitrite and IL-1ß, but not IL-6, were found in the plasma of sepsis survivors and this long-term systemic inflammation was not altered by the osmotic challenge. Moreover, the AVP and OT secretion (but not the osmolality) and c-fos expression in SON were significantly attenuated in CLP survivor animals. Additionally, there was no alteration in the water intake response induced by osmotic challenge in the sepsis survivor group. CONCLUSION: The results suggest that the inflammatory components mediated a persistent impairment in the component of the osmoregulatory reflex affecting the secretion of neurohypophyseal hormones in sepsis survivor animals.

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

PURPOSE: We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus. METHODS: Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies. RESULTS: The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group. CONCLUSIONS: We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Environmental enrichment reduces brain damage in hydrocephalic immature rats.

PURPOSE: We investigate the effects of environmental enrichment (EE) on morphological alterations in different brain structures of pup rats submitted to hydrocephalus condition. METHODS: Hydrocephalus was induced in 7-day-old pup rats by injection of 20% kaolin into the cisterna magna. Ventricular dilatation and magnetization transfer to analyze myelin were assessed by magnetic resonance. Hydrocephalic and control rats exposed to EE (n = 10 per group) were housed in cages with a tunnel, ramp, and colored plastic balls that would emit sound when touched. The walls of the housing were decorated with colored adhesive tape. Moreover, tactile and auditory stimulation was performed daily throughout the experiment. Hydrocephalic and control rats not exposed to EE (n = 10 per group) were allocated singly in standard cages. All animals were weighed daily and exposed to open-field conditions every 2 days until the end of the experiment when they were sacrificed and the brains removed for histology and immunohistochemistry. Solochrome cyanine staining was performed to assess the thickness of the corpus callosum. The glial fibrillary acidic protein method was used to evaluate reactive astrocytes, and the Ki67 method to assess cellular proliferation in the subventricular zone. RESULTS: The hydrocephalic animals exposed to EE showed better performance in Open Field tests (p < 0.05), while presenting lower weight gain. In addition, these animals showed better myelination as revealed by magnetization transfer (p < 0.05). Finally, the EE group showed a reduction in reactive astrocytes by means of glial fibrillary acidic protein immunostaining and preservation of the proliferation potential of progenitor cells. CONCLUSION: The results suggest that EE can protect the developing brain against damaging effects caused by hydrocephalus.

Curcumin suppresses inflammatory cytokines and heat shock protein 70 release and improves metabolic parameters during experimental sepsis.

CONTEXT: Curcumin has been reported to have anti-inflammatory, antioxidant and hypoglycaemic properties, besides reducing mortality in sepsis. OBJECTIVE: This study evaluates the biological activities of a curcumin dispersion formulated by spray-drying in experimental sepsis. MATERIALS AND METHODS: Male Wistar rats were subjected to sepsis by caecal ligation and puncture (CLP), controls were sham operated. The animals were treated with curcumin dispersion (100 mg/kg, p.o.) or water for 7 days prior to CLP and at 2 h after surgery. One group was used to analyze curcumin absorption through HPLC; another had the survival rate assessed during 48 h; and from a third group, blood was collected by decapitation to analyze metabolic and inflammatory parameters. RESULTS: The plasma curcumin levels reached 2.5 ng/mL at 4 h, dropped significantly (p < 0.001) at 6 h (1.2 ng/mL), and were undetectable at 24 h in both groups. Curcumin temporarily increased the survival rate of the septic rats by 20%. Moreover, it attenuated glycaemia (p < 0.05) and volemia (p < 0.05) alterations typically observed during sepsis, and decreased the levels of the proinflammatory cytokines IL-1ß and IL-6 in plasma (p < 0.001) and peritoneal lavage fluid (p < 0.05) of septic rats. Serum HSP70 levels were decreased (p < 0.01) at 24 h after CLP. DISCUSSION AND CONCLUSION: Our results show that the curcumin dispersion dose employed was not detrimental to the septic rats. In fact, it temporarily increased their survival rate, improved important metabolic parameters, reduced proinflammatory cytokines and HSP70 production.

Pre- and postshunting magnetization transfer ratios are in accordance with neurological and behavioral changes in hydrocephalic immature rats.

Hydrocephalus is a common neurological condition in children characterized by an imbalance between the production and absorption of cerebrospinal fluid (CSF), causing abnormal fluid accumulation in the brain cavities. Shunt systems have been used to drain excess CSF and to prevent progressive ventricular enlargement. However, despite improvements in these systems, neurological and structural changes cannot always be reversed. Our aim was to evaluate the magnetization transfer ratio as a biomarker for the effectiveness of a CSF shunt system to treat neurological and behavioral disorders observed in experimental hydrocephalus. Seven-day-old Wistar rats were used in this study. The pups were subjected to hydrocephalus induction via 20% kaolin intracisternal injection. After confirmation of ventriculomegaly by magnetic resonance imaging (MRI), a group of animals underwent placement of a ventriculosubcutaneous shunt (VSS). The reduction in ventricular size in hydrocephalic rats operated with functional VSS was observed as a decrease in ventricular ratio values and preservation of the corpus callosum thickness. Magnetization transfer values were significantly increased and matched to the recovery process of axonal myelination observed based on more-intense blue staining by solochrome cyanin. The histopathological analysis revealed a reduction in reactive astrocytes by means of GFAP immunostaining. The hydrocephalic rats operated with functional VSS also showed significant progress in motor and exploratory activities, similar to the control animals, at the end of the experiment. In conclusion, the VSS system employed 7 days after hydrocephalus induction was able to prevent structural damage and restore the axonal myelination process in periventricular structures by stabilizing and reducing the ventricular enlargement, and the results are in accordance with the magnetization transfer ratio in MRI.

Camellia sinensis neuroprotective role in experimentally induced hydrocephalus in Wistar rats.

PURPOSE: This study tested possible neuroprotective effects of Camellia sinensis-extracted polyphenols in experimental hydrocephalus in young rats. METHODS: Seven-day-old Wistar rats were used in this study. Pups were subjected to hydrocephalus induction by 20 % kaolin intracisternal injection. The polyphenol was administered intraperitoneally for 9 or 20 days from the induction of hydrocephalus. Clinical observations and behavioral tests were performed once a day. The animals, deeply anesthetized, were sacrificed by cardiac perfusion with saline 10 or 21 days after induction of hydrocephalus and their brains were removed. Preparations were made for histological analysis by hematoxylin and eosin, solochrome-cyanine, and immunohistochemistry for GFAP. RESULTS: Histopathological analysis showed that animals treated with the polyphenol for 9 consecutive days displayed reduction on astrocyte activity on the corpus callosum and external capsule, shown by GFAP immunostaining. They also displayed thicker and myelinated corpus callosum, exhibiting a more intense solochrome-cyanine blue staining. CONCLUSION: Although these results demonstrate a possible neuroprotective effect at the initial onset of the disease, additional studies should be performed to obtain an effective and safe therapy for deeper studies in clinical trials.

Optimization of HPV-positive women triage with p16/Ki67 dual staining cytology in an organized cervical cancer screening program in the center region of Portugal.

BACKGROUND: Organized cervical cancer (CxCa) screening is the most effective secondary prevention method to decrease the disease incidence and mortality. Screening for infection with 14 high-risk HPV genotypes (hrHPV) is recommended as primary screening test. Since only ca. 6 % of HPV-positive (HPV+) women will develop a high-grade lesion in 5 years, triage is critical for risk stratification and management of colposcopy resources. Dual staining (DS) p16/Ki67 cytology is an alternative to Papanicolau cytology (PAP) for triage of HPV+women, with potential improvements in sensitivity and specificity, and optimization of colposcopy referrals. OBJECTIVES: To compare PAP vs DS cytology in terms of (i) optimization of referrals for colposcopy and (ii) risk stratification to better define the follow-up interval. STUDY DESIGN: Retrospective analysis of the CxCa screening database of Centro Hospitalar Universitário de Coimbra (CHUC), one of the centralized diagnostic laboratories for the CxCa screening program of the central region of Portugal, between July 2019 and May 2023. At CHUC, since July 2019, all samples from hrHPV+women have been triaged with liquid PAP and tested with DS cytology. RESULTS: At baseline (1032 HPV+women), 1028 women were tested with DS: 739 women were DS negative (DS-) [70.7 % with normal PAP cytology (NILM) and 29.3 % with abnormal PAP cytology (ASC-US+)], and 289 were DS positive (DS+) (1.1 % NILM and 98.6 % ASC-US+). DS positivity as referral criterion for colposcopy instead of ASC-US+would have reduced the number of colposcopies by 39.4 % overall and by 48.3 % for other 12 hrHPV, while improving the number of colposcopies per HSIL (3.9 vs. 2.4 overall and 4.9 vs. 2.9 for other 12 hrHPV). In this cohort, if the follow-up interval for women positive for other 12 hrHPV+and DS- would have been extended from 1 to 3 years, 799 follow-up consultations, 799 HPV re-tests, and 277 colposcopies (-64.7 %) would have been avoided, with an overall risk of missed HSIL lesions of 2.2 %. CONCLUSIONS: Triage with DS allows the optimization of colposcopy referrals and a safe extension of the follow-up interval to 3 years for other 12 hrHPV+/DS- women, eliminating the need for annual re-testing for many women.

NLRP3 Activation Contributes to Memory Impairment in an Experimental Model of Pneumococcal Meningitis.

Bacterial meningitis is considered a life-threatening condition with high mortality rates. In response to the infection, signaling cascades, producing pro-inflammatory mediators trigger an exacerbated host immune response. Another inflammatory pathway occurs through the activation of inflammasomes. Studies highlight the role of the NLR family pyrin domain containing 3 (NLRP3) in central nervous system disorders commonly involved in neuroinflammation. We aimed to investigate the role of NLRP3 and its inhibitor MCC950 on neurochemical, immunological, and behavioral parameters in the early and late stages of experimental pneumococcal meningitis. For this, adult male Wistar rats received an intracisternal injection of Streptococcus pneumoniae or artificial cerebrospinal fluid as a placebo. The animals were divided into control/saline, control/MCC950, meningitis/saline, and meningitis/MCC950. Immediately after the meningitis induction, the animals received 140 ng/kg MCC950 via intracisternal injection. For the acute protocol, 24 h after induction, brain structures were collected to evaluate cytokines, NLRP3, and microglia. In the long-term group, the animals were submitted to open field and recognition of new objects tests at ten days after the meningitis induction. After the behavioral tests, the same markers were evaluated. The animals in the meningitis group at 24 h showed increased levels of cytokines, NLRP3, and IBA-1 expression, and the use of the MCC950 significantly reduced those levels. Although free from infection, ten days after meningitis induction, the animals in the meningitis group had elevated cytokine levels and demonstrated behavioral deficits; however, the single dose of NLRP3 inhibitor rescued the behavior deficits and decreased the brain inflammatory profile.

Sepsis compromises post-ischemic stroke neurological recovery and is associated with sex differences.

AIMS: Infection is a complication after stroke and outcomes vary by sex. Thus, we investigated if sepsis affects brain from ischemic stroke and sex involvement. MAIN METHODS: Male and female Wistar rats, were submitted to middle cerebral artery occlusion (MCAO) and after 7 days sepsis to cecal ligation and perforation (CLP). Infarct size, neuroinflammation, oxidative stress, and mitochondrial activity were quantified 24 h after CLP in the prefrontal cortex and hippocampus. Survival and neurological score were assessed up to 15 days after MCAO or 8 days after CLP (starting at 2 h after MCAO) and memory at the end. KEY FINDINGS: CLP decreased survival, increased neurological impairments in MCAO females. Early, in male sepsis following MCAO led to increased glial activation in the brain structures, and increased TNF-α and IL-1ß in the hippocampus. All groups had higher IL-6 in both tissues, but the hippocampus had lower IL-10. CLP potentiated myeloperoxidase (MPO) in the prefrontal cortex of MCAO male and female. In MCAO+CLP, only male increased MPO and nitrite/nitrate in hippocampus. Males in all groups had protein oxidation in the prefrontal cortex, but only MCAO+CLP in the hippocampus. Catalase decreased in the prefrontal cortex and hippocampus of all males and females, and MCAO+CLP only increased this activity in males. Female MCAO+CLP had higher prefrontal cortex complex activity than males. In MCAO+CLP-induced long-term memory impairment only in females. SIGNIFICANCE: The parameters evaluated for early sepsis after ischemic stroke show a worse outcome for males, while females are affected during long-term follow-up.

Chlamydial and Gonococcal Genital Infections: A Narrative Review.

Sexually transmitted infections (STIs) constitute one of the leading causes of disease burden worldwide, leading to considerable morbidity, mortality, health expenditures, and stigma. Of note are the most common bacterial STIs, chlamydial and gonococcal infections, whose etiological agents are Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), respectively. Despite being usually asymptomatic, in some cases these infections can be associated with long-term severe complications, such as pelvic inflammatory disease, chronic pelvic pain, infertility, ectopic pregnancy, and increased risk of other STIs acquisition. As the symptoms, when present, are usually similar in both infections, and in most of the cases these infections co-occur, the dual-test strategy, searching for both pathogens, should be preferred. In line with this, herein we focus on the main aspects of CT and NG infections, the clinical symptoms as well as the appropriate state-of-the-art diagnostic tests and treatment. Cost-effective strategies for controlling CT and NG infections worldwide are addressed. The treatment for both infections is based on antibiotics. However, the continuing global rise in the incidence of these infections, concomitantly with the increased risk of antibiotics resistance, leads to difficulties in their control, particularly in the case of NG infections. We also discuss the potential mechanism of tumorigenesis related to CT infections. The molecular bases of CT and NG infections are addressed, as they should provide clues for control or eradication, through the development of new drugs and/or effective vaccines against these pathogens.

Screening for diminished ovarian reserve in Portugal: a cost-saving answer to shorten the fertility journey.

Aim: Assess the budget impact of nationwide screening for diminished ovarian reserve (OR), via anti-Müllerian hormone (AMH) levels, to the Portugal National Health System (NHS). Patients & methods: The clinical journey was determined using literature and the family planning decision-making process/response using survey results. A panel of four local clinicians validated all assumptions/inputs. Results: Screening for OR led to an expected savings of € 9.4 million for the NHS, driven by a 24% reduction in medically assisted reproduction (MAR) use. When needed, referral for MAR was earlier and more women used first-line versus second-line techniques. The model estimated a 12% decrease in failure. Conclusion: This model shows AMH screening may allow more informed decisions, leading to a shorter fertility journey, more efficient use of treatments, and substantial cost-savings for the NHS.

Screening approaches for cervical cancer in Mozambique in HIV positive and negative women.

OBJECTIVE: Cervical cancer (CC) is a global health issue, in Mozambique, 5300 new cases and 3800 deaths are reported each year. The WHO recommends the introduction of HPV molecular testing for CC screening, but Mozambique uses an approach based on visual inspection with acetic acid (VIA). This study aims to evaluate the feasibility of high-risk HPV (hrHPV) testing compared to actual approaches in Mozambique. METHODS: An observational study was carried out in the DREAM center in Zimpeto, Mozambique. Women aged 30-55 were included. HPV testing was performed with the Cobas HPV test. They were then screened with the current national recommendations based on VIA. Cryotherapy was performed on-site or referred for colposcopy if necessary. RESULTS: In the period, 1207 women were enrolled, 47.8% HIV+; 124 (10.3%) VIA+, and HPV DNA test was positive in 325 (26.9%) women. HPV positivity rates were higher in HIV-infected women. In the sample, 52.8% of the 124 VIA+ women were HPV uninfected and underwent unnecessary cryotherapy or colposcopy. Meanwhile, 24.7% of the 1083 VIA- women were actually HPV infected. In comparison, a screen, triage and treat approach based on hrHPV testing would only test and treat the 325 HPV-infected women. CONCLUSION: The study found high rates of hrHPV infection, particularly in HIV-positive women, with many concurrent or multiple infections. The current screening method misses important hrHPV infections and results in many unnecessary treatments. These results support the use of HPV molecular testing as the initial screening test for CC.

Bacterial meningitis in Africa.

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group B Streptococcus), Escherichia coli, and Staphylococcus aureus are neonatal meningitis's most common causal agents. Despite efforts to vaccinate against the most common causes of bacterial neuro-infections, bacterial meningitis remains a significant cause of mortality and morbidity in Africa, with children below 5 years bearing the heaviest disease burden. The factors attributed to this continued high disease burden include poor infrastructure, continued war, instability, and difficulty in diagnosis of bacterial neuro-infections leading to delay in treatment and hence high morbidity. Despite having the highest disease burden, there is a paucity of African data on bacterial meningitis. In this article, we discuss the common etiologies of bacterial neuroinfectious diseases, diagnosis and the interplay between microorganisms and the immune system, and the value of neuroimmune changes in diagnostics and therapeutics.