We analyzed an EGFR-mutated lung cancer with a pathologic diagnosis of combined large cell neuroendocrine carcinoma with mixed adenocarcinoma subtypes. Targeted next-generation sequencing of each component suggested that mutations in RB1, TP53, and SMAD4 and apparent loss of heterozygosity of TP53 and SMAD4 accompanied the transition of different adenocarcinoma subtypes. Additional gene mutations including PTEN, MST1R, and PIK3CA were noted during transdifferentiation from acinar adenocarcinoma to large cell neuroendocrine carcinoma. Combined DNA and RNA analysis using Todai OncoPanel revealed that transdifferentiation to different pathologic subtypes occurred in a single tumor through the accumulation of gene mutations.

Keywords: Case report; Clonal analysis; EGFR; Gene mutations; NSCLC; Pathologic subtypes.

Antitumor necrosis factor-associated nontuberculous mycobacteria-immune reconstitution inflammatory syndrome (IRIS) has rarely been reported. An 84-year-old woman with a history of rheumatoid arthritis treated with etanercept was diagnosed with Mycobacterium avium complex (MAC) pulmonary disease six years before admission. Etanercept was discontinued two years ago because of MAC pulmonary disease progression and restarted nine months before admission because of worsening arthritis, again resulting in MAC pulmonary disease progression. Etanercept was discontinued again; however, the pulmonary disease progressed more rapidly. The condition was considered paradoxical worsening caused by IRIS due to etanercept discontinuation. The disease resolved quickly with chemotherapy for MAC.

Keywords: Antitumor necrosis factor therapy; CT, computed tomography; HIV, human immunodeficiency virus; IRIS, immune reconstitution inflammatory syndrome; Immune reconstitution inflammatory syndrome; MAC, Mycobacterium avium complex; Mycobacterium avium complex; NTM, nontuberculous mycobacteria; Nontuberculous mycobacteria; Paradoxical response; TNF, tumor necrosis factor; Tumor necrosis factor-α.

We report a case of severe uveitis flare-up with iridis rubeosis recurrence and cystoid macular edema early after the first BioNTech-Pfizer COVID-19 vaccination in a 17-year-old boy. We also performed a systematic literature review on ocular inflammation after COVID-19 vaccinations.

Keywords: BioNTech-Pfizer; COVID-19; Comirnaty; Cystoid macular edema; Uveitis; Vaccine.

Keywords: adverse reaction; allergy; complication; cosmetic; permanent makeup; pigment; tattoo.

Background: HIV-TB treatment integration reduces mortality. Operational implementation of integrated services is challenging. This study assessed the impact of quality improvement (QI) for HIV-TB integration on mortality within primary healthcare (PHC) clinics in South Africa.

Methods: An open-label cluster randomized controlled study was conducted between 2016 and 2018 in 40 rural clinics in South Africa. The study statistician randomized PHC nurse-supervisors 1:1 into 16 clusters (eight nurse-supervisors supporting 20 clinics per arm) to receive QI, supported HIV-TB integration intervention or standard of care (control). Nurse supervisors and clinics under their supervision, based in the study health districts were eligible for inclusion in this study. Nurse supervisors were excluded if their clinics were managed by municipal health (different resource allocation), did not offer co-located antiretroviral therapy (ART) and TB services, services were performed by a single nurse, did not receive non-governmental organisation (NGO) support, patient data was not available for > 50% of attendees. The analysis population consists of all patients newly diagnosed with (i) both TB and HIV (ii) HIV only (among patients previously treated for TB or those who never had TB before) and (iii) TB only (among patients already diagnosed with HIV or those who were never diagnosed with HIV) after QI implementation in the intervention arm, or enrolment in the control arm. Mortality rates was assessed 12 months post enrolment, using unpaired t-tests and cox-proportional hazards model. (Clinicaltrials.gov, NCT02654613, registered 01 June 2015, trial closed).

Findings: Overall, 21 379 participants were enrolled between December 2016 and December 2018 in intervention and control arm clinics: 1329 and 841 HIV-TB co-infected (10·2%); 10 799 and 6 611 people living with Human Immunodeficiency Virus (HIV)/ acquired immunodeficiency syndrome (AIDS) (PLWHA) only (81·4%); 1 131 and 668 patients with TB only (8·4%), respectively. Average cluster sizes were 1657 (range 170-5782) and 1015 (range 33-2027) in intervention and control arms. By 12 months, 6529 (68·7%) and 4074 (70·4%) were alive and in care, 568 (6·0%) and 321 (5·6%) had completed TB treatment, 1078 (11·3%) and 694 (12·0%) were lost to follow-up, with 245 and 156 deaths occurring in intervention and control arms, respectively. Mortality rates overall [95% confidence interval (CI)] was 4·5 (3·4-5·9) in intervention arm, and 3·8 (2·6-5·4) per 100 person-years in control arm clusters [mortality rate ratio (MRR): 1·19 (95% CI 0·79-1·80)]. Mortality rates among HIV-TB co-infected patients was 10·1 (6·7-15·3) and 9·8 (5·0-18·9) per 100 person-years, [MRR: 1·04 (95% CI 0·51-2·10)], in intervention and control arm clusters, respectively.

Interpretation: HIV-TB integration supported by a QI intervention did not reduce mortality in HIV-TB co-infected patients. Demonstrating mortality benefit from health systems process improvements in real-world operational settings remains challenging. Despite the study being potentially underpowered to demonstrate the effect size, integration interventions were implemented using existing facility staff and infrastructure reflecting the real-world context where most patients in similar settings access care, thereby improving generalizability and scalability of study findings.

Funding: Research reported in this publication was supported by South African Medical Research Council (SAMRC), and UK Government's Newton Fund through United Kingdom Medical Research Council (UKMRC).

Keywords: Cluster randomized trial; HIV; Mortality; Primary healthcare; Quality improvement; TB/HIV integration.

Background: Ultrasound guided-deep serratus anterior plane block (USG-DSAPB) has been used for pain management of patients undergoing modified radical mastectomy (MRM), but evidence supporting their adjuvant analgesic benefits is limited. We explored the efficacy and safety of preemptive use of ropivacaine combined with different doses of dexmedetomidine (DEX) in USG-DSAPB for patients undergoing MRM.

Methods: Ninety-five female patients undergoing unilateral MRM were allocated randomly to two groups. Group RD1 had 20 mL of 0.5% ropivacaine with 5 mg of dexamethasone and 0.5 μg·kg^-1 DEX in USG-DSAPB. Group RD2 had 20 mL of 0.5% ropivacaine with 5 mg of dexamethasone and 1 μg·kg^-1 DEX in USG-DSAPB. The primary outcome was sufentanil consumption 72 h after USG-DSAPB. Secondary outcomes were: postoperative pain scores and level of sedation; intraoperative hemodynamics; duration of post-anesthesia care unit (PACU) stay; prevalence of moderate-to-severe pain; one-time puncture success; procedure time of blockade; time to first rescue analgesia; requirement of rescue analgesia; satisfaction scores of patients and surgeons; duration of hospital stay; adverse events; prevalence of chronic pain; quality of postoperative functional recovery.

Results: Compared with the RD1 group, the visual analog scale score for coughing was significantly lower at 4, 8, 12 h and sufentanil consumption was significantly lower at 4, 8, 12, 24, and 48 h after surgery in the RD2 group (P < 0.05). The time to first rescue analgesia was significantly longer in the RD2 group (P < 0.05). The requirement for rescue analgesia was significantly higher in the RD1 group (P < 0.05). The prevalence of moderate-to-severe pain, number of patients using vasoactive agents, duration of PACU stay, as well as consumption of propofol, remifentanil, and DEX were significantly lower in the RD2 group (P < 0.05). There were no significant differences between the two groups with respect to one-time puncture success, procedure time of blockade, total dermatomal spread, satisfaction scores of patients and surgeons, postoperative complications, duration of hospital stay, 40-item Quality of Recovery questionnaire (QoR-40) score, or prevalence of chronic pain (P > 0.05).

Conclusions: We discovered that 1 μg·kg^-1 (not 0.5 μg·kg^-1) DEX combined with 20 mL of 0.5% ropivacaine and 5 mg of dexamethasone in USG-DSAPB could provide superior postoperative analgesia for patients undergoing MRM. However, the quality of postoperative functional recovery and prevalence of chronic pain were similar.Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=54929, identifier: ChiCTR2000033685.

Keywords: dexmedetomidine; modified radical mastectomy; ropivacaine; serratus anterior plane block; ultrasound.

Direct oral anticoagulant (DOAC) reversal before intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients is well-documented in Europe, specifically for dabigatran: the selective humanized monoclonal antibody fragment idarucizumab, given to neutralize dabigatran prior to IVT, was associated with improved outcomes post-IVT. However, in the United States, this approach is rarely reported and not endorsed by guidelines. Therefore, further reporting on this is needed and neuroradiographic correlation may help validate this concept. At our hospital in Tampa, Florida, two octogenarians with atrial fibrillation, adherent with the DOAC dabigatran, presented with AIS shortly after symptom onset. Both received idarucizumab, then IVT. Clinical outcomes, treatment times, and perfusion-based neuroradiographic parameters were assessed. Patient A had a 41 ml penumbra on computed tomography perfusion (CTP) scan that decreased to 15 ml in final infarct volume on follow-up imaging, resulting in a 26 ml penumbral salvage (63.4%), and National Institutes of Health Stroke Scale (NIHSS) improved from 11 to 9 . Patient B had a 23 ml penumbra on CTP that decreased to 0.5 ml on follow-up imaging, resulting in a 22.5 ml penumbral salvage (97.8%), and NIHSS improved from 9 to 4. Neither developed bleeding complications. Both had delayed door-to-needle times but nevertheless demonstrated clinical neurological improvements. In our limited experience, IVT after immediate DOAC reversal in AIS patients on dabigatran was associated with clinical improvement in NIHSS by 2 to 5 points (with no neuroworsening), and penumbral salvage of ischemic brain tissue on neuroimaging ranging from 63.4% to 97.8%. Further reporting on this may lead to greater IVT use and better outcomes in "DOAC failures", especially for patients without other acute treatment options such as mechanical thrombectomy. Research into other anticoagulant reversal agents pre-IVT in AIS is also warranted.

Keywords: anticoagulation reversal; anticoagulation therapy; atrial fibrillation; ischemic stroke; thrombolytic.

We report a case of FLT3-mutated AML with t(6;9) in which induction chemotherapy with DA and midostaurin failed to achieve complete cytogenetic or molecular remission. Due to the COVID-19 pandemic and co-existing cellulitis, monotherapy with the selective FLT3-inhibitor gilteritinib was used as an alternative consolidation treatment option rather than further intensive chemotherapy. Gilteritinib was able to achieve complete molecular and cytogenetic remission despite the additional cytogenetic abnormality. This case provides supporting evidence for the use of single agent gilteritinib in high-risk primary refractory FLT3-mutated AML with t(6;9) prior to transplantation.

Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency due to defect in various genes leading to an increase in susceptibility to skin and mucosal infection. Mutation in signal transducer and activator of transcription 1 (STAT 1) gene being the most common cause of CMC can lead to increased risk of infections, multisystem abnormalities, and malignancy. We describe a 27 year old Indian woman with clinical features of CMC including esophageal stenosis, gangrene of the finger, endocrinological and immunological abnormalities and STAT1 mutation (p.Leu407Val). She was treated with antifungals which led to symptomatic improvement.

Keywords: Candida albicans; Candida parapsilosis; chronic mucocutaneous candidiasis; signal transducer and activator of transcription 1 (STAT 1) mutation.

Purpose: Facial dog bites often cause periorbital trauma; however, the globe is rarely damaged. Most globe injury following dog bites results from unusual circumstances and typically presents with concomitant periorbital and ocular adnexal injuries.

Observations: The case presented is a rare presentation of isolated globe rupture without orbital trauma following facial dog bite in a child without history or evidence of decreased blink reflex, mental deficiency, or substance use.

Conclusions and importance: Ophthalmic investigation is warranted in all pediatric periorbital dog bite injuries, even in the setting of minimal or absent periorbital trauma. As additional blunt trauma to the globe in the immediate recovery period resulted in a second open globe injury, the critical importance of protective eyewear, activity restriction, and judicious corneal suture removal postoperatively following repair of open globe injury is discussed.

Keywords: Corneal laceration; Dog bite; Open globe injury; Pet trauma.

Alzheimer's disease is pathologically characterized by abnormal accumulation of amyloid-beta plaques, neurofibrillary tangles, oxidative stress, neuroinflammation, and neurodegeneration. Metal dysregulation, including excessive zinc released by presynaptic neurons, plays an important role in tau pathology and oxidase activation. The activities of mammalian target of rapamycin (mTOR)/ribosomal S6 protein kinase (p70S6K) are elevated in the brains of patients with Alzheimer's disease. Zinc induces tau hyperphosphorylation via mTOR/P70S6K activation in vitro. However, the involvement of the mTOR/P70S6K pathway in zinc-induced oxidative stress, tau degeneration, and synaptic and cognitive impairment has not been fully elucidated in vivo. Here, we assessed the effect of pathological zinc concentrations in SH-SY5Y cells by using biochemical assays and immunofluorescence staining. Rats (n = 18, male) were laterally ventricularly injected with zinc, treated with rapamycin (intraperitoneal injection) for 1 week, and assessed using the Morris water maze. Evaluation of oxidative stress, tau phosphorylation, and synaptic impairment was performed using the hippocampal tissue of the rats by biochemical assays and immunofluorescence staining. The results from the Morris water maze showed that the capacity of spatial memory was impaired in zinc-treated rats. Zinc sulfate significantly increased the levels of P-mTOR Ser2448, P-p70S6K Thr389, and P-tau Ser356 and decreased the levels of nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in SH-SY5Y cells and in zinc-treated rats compared with the control groups. Increased expression of reactive oxygen species was observed in zinc sulfate-induced SH-SY5Y cells and in the hippocampus of zinc-injected rats. Rapamycin, an inhibitor of mTOR, rescued zinc-induced increases in mTOR/p70S6K activation, tau phosphorylation, and oxidative stress, and Nrf2/HO-1 inactivation, cognitive impairment, and synaptic impairment reduced the expression of synapse-related proteins in zinc-injected rats. In conclusion, our findings imply that rapamycin prevents zinc-induced cognitive impairment and protects neurons from tau pathology, oxidative stress, and synaptic impairment by decreasing mTOR/p70S6K hyperactivity and increasing Nrf2/HO-1 activity.

Keywords: animal model; Nrf2/HO-1 (nuclear factor erythroid 2-related factor-2/heme oxygenase-1); cognitive deficit; mTOR/p70S6K pathway; oxidative stress; rapamycin; tau hyperphosphorylation; zinc.

The use and socio-environmental importance of fruits dramatically changed after the emergence of arboriculture and fruit domestication in the eastern Mediterranean, between the 5th and the 3rd millennia BCE. Domesticated fruits together with cultivation techniques apparently reached the western Mediterranean via colonial activities during the 1st millennium BCE - early 1st millennium CE. However, the pace and chronology of this diffusion as well as the recompositions in diversity, to adapt to new socio-environmental conditions, remain poorly known. In this study we investigate archaeobotanical records in Southern France from the Neolithic to the end of the Roman empire (ca. 5,800 BCE - 500 CE) to assess changes in fruit use as well as the emergence, spread and evolution of fruit cultivation. We explore changes in native traditions faced with innovations brought by Mediterranean colonization and how domesticated fruit cultivation spread from the Mediterranean to more temperate areas. Archaeobotanical data from 577 assemblages were systematically analyzed distinguishing two datasets according to preservation of plant remains (charred vs. uncharred), as this impacts on the quantity and diversity of taxa. The 47 fruit taxa identified were organized in broad categories according to their status and origin: exotic, allochtonous cultivated, indigenous cultivated, wild native. We also analyzed diversity, quantity of fruits compared to the total of economic plants and spatio-temporal variations in the composition of fruit assemblages using correspondence factor analyses. Archaeobotanical data reflect variations and continuities in the diversity of species used through time and space. In the Mediterranean area, significant changes related to the arrival of new plants and development of fruit cultivation occurred mainly, first during the Iron Age (6th-5th c. BCE), then in the beginning of the Roman period. Large cities played a major role in this process. In agreement with archeological information, archaeobotanical data reveal the predominance of viticulture in both periods. However, arboriculture also included other fruit species that have been subject to less intensive and specialized cultivation practices. Most significantly, this study pinpoints the continuous contribution of native, supposedly wild fruits throughout the chronology. Despite the homogenizing Roman influence, results reveal clear differences between the Mediterranean and temperate regions.

Keywords: Mediterranean; arboriculture; archaeobotany; biogeography; diffusion; domestication; fruit uses; management practices.

The facultative intracellular pathogen Listeria monocytogenes is of major veterinary importance in small ruminants. Nevertheless, details of L. monocytogenes interactions with cells of small ruminants are not fully established. To study the potential of L. monocytogenes to infect sheep cells, we used the finite sheep kidney cell line (shKEC), which was infected with the wild-type L. monocytogenes strain EGDe. The invasion efficiency was 0.015 ± 0.004%. The invasion factor InlB was critically important for invasion, and inlB gene deletion almost prevented L. monocytogenes invasion into shKEC cells. Comparison of the potential of phylogenetically defined InlB isoforms to restore the invasive phenotype of the EGDeΔinlB strain demonstrated that although all InlB isoforms restored invasion of the EGDeΔinlB strain into shKEC cells, the InlB isoforms typical of highly virulent ruminant strains of the clonal complexes CC1 and CC7 were more efficient than isoforms typical of CC2 and CC9 strains (which are less virulent toward ruminants) in supporting invasion. Listeria monocytogenes effectively multiplied with a doubling of time in about 90 min after they entered the sheep cells. Intracellular bacteria moved using the well-known actin polymerization mechanism. Cell-to-cell spreading was restricted to the infection of a few tens of neighboring cells for 7 days. Overall, the obtained results demonstrated that (i) InlB is required for invasion into sheep cells, (ii) InlB isoforms might be important for hypervirulence of certain clonal groups toward ruminants, and (iii) L. monocytogenes effectively multiplies in ovine cells once entered.

Keywords: InlB; Listeria monocytogenes; clonal complex; invasion factor; listeriosis; small ruminants.

Diabetes during pregnancy is associated with elevated maternal insulin, leptin and IL-6. Within the placenta, IL-6 can further stimulate leptin production. Despite structural similarities and shared roles in inflammation, leptin and IL-6 have contrasting effects on neurodevelopment, and the relative importance of maternal diabetes or chorioamnionitis on fetal hormone exposure has not been defined. We hypothesized that there would be a positive correlation between IL-6 and leptin with progressively increased levels in pregnancies complicated by maternal diabetes and chorioamnionitis. To test this hypothesis, cord blood samples were obtained from 104 term infants, including 47 exposed to maternal diabetes. Leptin, insulin, and IL-6 were quantified by multiplex assay. Factors independently associated with hormone levels were identified by univariate and multivariate linear regression. Unlike IL-6, leptin and insulin were significantly increased by maternal diabetes. Maternal BMI and birth weight were independent predictors of leptin and insulin with birth weight the strongest predictor of leptin. Clinically diagnosed chorioamnionitis and neonatal sepsis were associated with increased IL-6 but not leptin. Among appropriate for gestational age infants without sepsis, IL-6 and leptin were strongly correlated (R=0.6, P<0.001). In summary, maternal diabetes and birth weight are associated with leptin while chorioamnionitis is associated with IL-6. The constraint of the positive association between leptin and IL-6 to infants without sepsis suggests that the term infant and placenta may have a limited capacity to increase cord blood levels of the neuroprotective hormone leptin in the presence of increased cord blood levels of the potential neurotoxin IL-6.

Keywords: adipokine cytokine; development; inflammation; insulin; neonatal; obesity; sepsis.

The pathogenic bacterium Ralstonia solanacearum caused tomato bacterial wilt (TBW), a destructive soil-borne disease worldwide. There is an urgent need to develop effective control methods. Myxobacteria are microbial predators and are widely distributed in the soil. Compared with other biocontrol bacteria that produce antibacterial substances, the myxobacteria have great potential for biocontrol. This study reports a strain of Myxococcus xanthus R31 that exhibits high antagonistic activity to R. solanacearum. Plate test indicated that the strain R31 efficiently predated R. solanacearum. Pot experiments showed that the biocontrol efficacy of strain R31 against TBW was 81.9%. Further study found that the secreted protein precipitated by ammonium sulfate had significant lytic activity against R. solanacearum cells, whereas the ethyl acetate extract of strain R31 had no inhibitory activity against R. solanacearum. Substrate spectroscopy assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of secreted proteins showed that some peptidases, lipases, and glycoside hydrolases might play important roles and could be potential biocontrol factors involved in predation. The present study reveals for the first time that the use of strain M. xanthus R31 as a potential biocontrol agent could efficiently control TBW by predation and secreting extracellular lyase proteins.

Keywords: Myxococcus xanthus R31; Ralstonia solanacearum; biocontrol; extracellular proteins; predation; tomato bacteria wilt.

Aim: This study aims to evaluate the effect of endometrial polyp resection by office hysteroscopy during in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle on pregnancy rate.

Setting and design: A retrospective observational study (case series).

Materials and methods: Twenty-five patients from a total of 346 patients that started IVF/ICSI treatment due to different causes of infertility over the period from January 2018 to December 2019 underwent an office hysteroscopy during ovarian stimulation (day 7-8) due to suspected endometrial polyp by transvaginal ultrasound and confirmed at day 7 of ovarian stimulation were retrospectively investigated.

Results: Eighteen patients from the 25 patients that started IVF/ICSI treatment; endometrial polyp was confirmed by office hysteroscopy and resected, egg collection performed after 4-5 days after the hysteroscopy, embryo transfer done Double ET) at Day 3 and 5, the clinical Pregnancy rate was 56% (10 from the 18). No hysteroscopy-related adverse events were reported.

Conclusion: Office hysteroscopy during ovarian stimulation in the IVF/ICSI treatment cycle may be useful in confirming the diagnosis and resection of endometrial polyp suspected by transvaginal ultrasound and is safe on the endometrium in terms of receptivity and improvement of the pregnancy rate. As the sample size of our study is relatively small, a well-designed large RCT is required to confirm our results before clinical advice is released.

Keywords: Endometrial polyp; in vitro fertilization and hysteroscopy; infertility.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases that affect synovitis, bone, cartilage, and joint. RA leads to bone and cartilage damage and extra-articular disorders. However, the pathogenesis of RA is still unclear, and the lack of effective early diagnosis and treatment causes severe disability, and ultimately, early death. Accumulating evidence revealed that the regulatory network that includes long non-coding RNAs (lncRNAs)/circular RNAs (circRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNA) plays important roles in regulating the pathological and physiological processes in RA. lncRNAs/circRNAs act as the miRNA sponge and competitively bind to miRNA to regulate the expression mRNA in synovial tissue, FLS, and PBMC, participate in the regulation of proliferation, apoptosis, invasion, and inflammatory response. Thereby providing new strategies for its diagnosis and treatment. In this review, we comprehensively summarized the regulatory mechanisms of lncRNA/circRNA-miRNA-mRNA network and the potential roles of non-coding RNAs as biomarkers and therapeutic targets for the diagnosis and treatment of RA.

Keywords: circRNA; lncRNA; miRNA; noncoding RNA; review; rheumatoid arthritis.

Keywords: CB1 receptor degradation; CB2 receptor biased signaling; beta cell function; chronic kidney disease; endocannabinoids; fibrosis; pregnancy-parturition; white adipose tissue.

[This corrects the article DOI: 10.17912/micropub.biology.000504.].

Multiferroic materials have attracted wide interest because of their exceptional static^1-3 and dynamical^4-6 magnetoelectric properties. In particular, type-II multiferroics exhibit an inversion-symmetry-breaking magnetic order that directly induces ferroelectric polarization through various mechanisms, such as the spin-current or the inverse Dzyaloshinskii-Moriya effect^3,7. This intrinsic coupling between the magnetic and dipolar order parameters results in high-strength magnetoelectric effects^3,8. Two-dimensional materials possessing such intrinsic multiferroic properties have been long sought for to enable the harnessing of magnetoelectric coupling in nanoelectronic devices^1,9,10. Here we report the discovery of type-II multiferroic order in a single atomic layer of the transition-metal-based van der Waals material NiI₂. The multiferroic state of NiI₂ is characterized by a proper-screw spin helix with given handedness, which couples to the charge degrees of freedom to produce a chirality-controlled electrical polarization. We use circular dichroic Raman measurements to directly probe the magneto-chiral ground state and its electromagnon modes originating from dynamic magnetoelectric coupling. Combining birefringence and second-harmonic-generation measurements with theoretical modelling and simulations, we detect a highly anisotropic electronic state that simultaneously breaks three-fold rotational and inversion symmetry, and supports polar order. The evolution of the optical signatures as a function of temperature and layer number surprisingly reveals an ordered magnetic polar state that persists down to the ultrathin limit of monolayer NiI₂. These observations establish NiI₂ and transition metal dihalides as a new platform for studying emergent multiferroic phenomena, chiral magnetic textures and ferroelectricity in the two-dimensional limit.