Epidemiological characteristics of cryptococcal meningoencephalitis associated with Cryptococcus neoformans var. grubii from HIV-infected patients in Madagascar : a cross-sectional study

Cryptococcal meningoencephalitis (CM) remains the most prevalent invasive fungal infection worldwide. The main objective of this study was to describe the prevalence of CM and cryptococcal infection in HIV-infected patients in Madagascar. The secondary objectives were to assess the adjusted prevalence of CM according to clinical presentation and patient characteristics, to determine crude 90-day survival according to cryptococcal antigen (CrAg) status and CM, and to identify the genotypes of Cryptococcus clinical isolates. This cross-sectional study was carried out at two urban hospitals in Antananarivo (central highlands) and Toamasina (east coast) between November 2014 and December 2016. Consecutive HIV-infected adults presenting with CD4 cell counts 64200/\u3bcl were enrolled. Lateral flow immunoassays of CrAg were performed on serum for all patients, and on cerebrospinal fluid for patients with CM symptoms. MALDI-ToF MS, ITS sequencing, and determinations of the molecular and mating types of the isolates were performed. Fluconazole is the only drug for CM treatment available in Madagascar. Patients were treated orally, with high doses (1200 mg/day) for 10-12 weeks and then with 200 mg/day. Minimum inhibitory concentrations were determined for amphotericin B, flucytosine, voriconazole and fluconazole in E-tests. Overall prevalence was 13.2% (95% CI 7.9-20.3) for cryptococcal infection and 10.9% (95% CI 6.1-17.5) for CM, among the 129 HIV-infected patients studied. The 90-day mortality rate was 58.8% (10/17) in CrAg-positive patients and 17.9% (20/112) in CrAg-negative patients (p<0.001). The 13 Cryptococcus strains obtained at baseline were all Cryptococcus neoformans var. grubii, genotypes VNI-\u3b1A (3 isolates), VNII-\u3b1A (4 isolates) or hybrid VNI/VNII-\u3b1AA\u3b1 (6 isolates), suggesting high diversity. Two strains acquired fluconazole resistance after four and five months of exposure, respectively. The prevalence of cryptococcosis is high in Madagascar and this serious condition is life-threatening in HIV-infected patients. These findings will be used to raise the awareness of national authorities to strengthen the national HIV/AIDS control program

Sex-differences in the longitudinal recovery of neuromuscular function in COVID-19 associated acute respiratory distress syndrome survivors

Introduction: Patients admitted to the intensive care unit (ICU) following severe acute respiratory syndrome 2 (SARS-CoV-2) infection may have muscle weakness up to 1 year or more following ICU discharge. However, females show greater muscle weakness than males, indicating greater neuromuscular impairment. The objective of this work was to assess sex differences in longitudinal physical functioning following ICU discharge for SARS-CoV-2 infection. Methods: We performed longitudinal assessment of physical functioning in two groups: 14 participants (7 males, 7 females) in the 3-to-6 month and 28 participants (14 males, 14 females) in the 6-to-12 month group following ICU discharge and assessed differences between the sexes. We examined self-reported fatigue, physical functioning, compound muscle action potential (CMAP) amplitude, maximal strength, and the neural drive to the tibialis anterior muscle. Results: We found no sex differences in the assessed parameters in the 3-to-6-month follow-up, indicating significant weakness in both sexes. Sex differences emerged in the 6-to-12-month follow-up. Specifically, females exhibited greater impairments in physical functioning, including lower strength, walking lower distances, and high neural input even 1 year following ICU-discharge. Discussion: Females infected by SARS-CoV-2 display significant impairments in functional recovery up to 1 year following ICU discharge. The effects of sex should be considered in post-COVID neurorehabilitation

Parallelizable MACs Based on the Sum of PRPs with Security Beyond the Birthday Bound

The combination of universal hashing and encryption is a fundamental paradigm for the construction of symmetric-key MACs, dating back to the seminal works by Wegman and Carter, Shoup, and Bernstein. While fully sufficient for many practical applications, the Wegman-Carter construction, however, is well-known to break if nonces are ever repeated, and provides only birthday-bound security if instantiated with a permutation. Those limitations inspired the community to several recent proposals that addressed them, initiated by Cogliati et al.\u27s Encrypted Wegman-Carter Davies-Meyer (EWCDM) construction. This work extends this line of research by studying two constructions based on the sum of PRPs: (1) a stateless deterministic scheme that uses two hash functions, and (2) a nonce-based scheme with one hash-function call and a nonce. We show up to 2n/3-bit security for both of them if the hash function is universal. Compared to the EWCDM construction, our proposals avoid the fact that a single reuse of a nonce can lead to a break

Full Indifferentiable Security of the Xor of Two or More Random Permutations Using the χ2\chi^2 Method

The construction $\mathsf{XORP}$ (bitwise-xor of outputs of two independent $n$-bit random permutations) has gained broad attention over the last two decades due to its high security. Very recently, Dai \textit{et al.} (CRYPTO\u2717), by using a method which they term the {\em Chi-squared method} ($\chi^2$ method), have shown $n$-bit security of $\mathsf{XORP}$ when the underlying random permutations are kept secret to the adversary. In this work, we consider the case where the underlying random permutations are publicly available to the adversary. The best known security of $\mathsf{XORP}$ in this security game (also known as {\em indifferentiable security}) is $\frac{2n}{3}$-bit, due to Mennink \textit{et al.} (ACNS\u2715). Later, Lee (IEEE-IT\u2717) proved a better $\frac{(k-1)n}{k}$-bit security for the general construction $\mathsf{XORP}[k]$ which returns the xor of $k$ ($\geq 2$) independent random permutations. However, the security was shown only for the cases where $k$ is an even integer. In this paper, we improve all these known bounds and prove full, {\em i.e.,} $n$-bit (indifferentiable) security of $\mathsf{XORP}$ as well as $\mathsf{XORP}[k]$ for any $k$. Our main result is $n$-bit security of $\mathsf{XORP}$, and we use the $\chi^2$ method to prove it

Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes

It has been found that CDKL5 gene mutations are responsible for early-onset epilepsy and drug resistance. We screened a population of 92 patients with classic/atypical Rett syndrome, 17 Angelman/Angelman-like patients and six idiopathic autistic patients for CDKL5 mutations and exon deletions and identified seven novel mutations: six in the Rett subset and one in an Angelman patient. This last, an insertion in exon 11, c.903_904 dupGA, p.Leu302Aspfx49X, is associated with a relatively mild clinical presentation as the patient is the only one capable of sitting and walking alone. Of the six mutations, two are de novo missense changes affecting highly conserved aminoacid residues, c.215 T > C p.Ile72Thr and c.380A > G p.His127Arg (present in a mosaic condition) found in two girls with the most severe clinical presentation, while the remaining are the splicing c.145 + 2 T > C and c.2376 + 5G > A, the c.1648C > T p.Arg550X and the MPLA-identified c.162_99del261 mutation. RNA characterisation of four mutations revealed the aberrant transcript of the missense allele (case 2) and not the stop mutation (case 3), but also allowed the splicing mutation (case 1) and the c.-162_99del261 (case 4) to be ategorised as truncating. The obtained data reinforce the view that a more severe phenotype is due more to an altered protein than haploinsufficiency. Furthermore, the mutational repertoire of the CDKL5 gene is shown to be expanded by testing patients with phenotypical overlap to Rett syndrome and applying multiplex ligation-dependent probe amplification

Salinity effects on plasma ion levels, cortisol, and osmolality in Chinook salmon following lethal sampling

Studies on hydromineral balance in fishes frequently employ measurements of electrolytes following euthanasia. We tested the effects of fresh- or salt-water euthanasia baths of tricaine mesylate (MS-222) on plasma magnesium (Mg²⁺) and sodium (Na⁺) ions, cortisol and osmolality in fish exposed to saltwater challenges, and the ion and steroid hormone fluctuations over time following euthanasia in juvenile spring Chinook salmon (Oncorhynchus tshawytscha). Salinity of the euthanasia bath affected plasma Mg²⁺ and Na⁺ concentrations as well as osmolality, with higher concentrations in fish euthanized in saltwater. Time spent in the bath positively affected plasma Mg²⁺ and osmolality, negatively affected cortisol, and had no effect on Na⁺ concentrations. The difference of temporal trends in plasma Mg²⁺ and Na⁺ suggests that Mg²⁺ may be more sensitive to physiological changes and responds more rapidly than Na⁺. When electrolytes and cortisol are measured as endpoints after euthanasia, care needs to be taken relative to time after death and the salinity of the euthanasia bathThis is the publisher’s final pdf. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/comparative-biochemistry-and-physiology-part-a-molecular-and-integrative-physiology/Keywords: Magnesium, Saltwater challenge, Smolt, MS-222, Cortisol, Delayed sampling, Osmoregulation, Oncorhynchus tshawytscha, Euthanasia, SodiumKeywords: Magnesium, Saltwater challenge, Smolt, MS-222, Cortisol, Delayed sampling, Osmoregulation, Oncorhynchus tshawytscha, Euthanasia, Sodiu

Encrypt or Decrypt? To Make a Single-Key Beyond Birthday Secure Nonce-Based MAC

In CRYPTO 2016, Cogliati and Seurin have proposed a highly secure nonce-based MAC called Encrypted Wegman-Carter with Davies-Meyer ($\textsf{EWCDM}$) construction, as $\textsf{E}_{K_2}\bigl(\textsf{E}_{K_1}(N)\oplus N\oplus \textsf{H}_{K_h}(M)\bigr)$ for a nonce $N$ and a message $M$. This construction achieves roughly $2^{2n/3}$ bit MAC security with the assumption that $\textsf{E}$ is a PRP secure $n$-bit block cipher and $\textsf{H}$ is an almost xor universal $n$-bit hash function. In this paper we propose Decrypted Wegman-Carter with Davies-Meyer ($\textsf{DWCDM}$) construction, which is structurally very similar to its predecessor $\textsf{EWCDM}$ except that the outer encryption call is replaced by decryption. The biggest advantage of $\textsf{DWCDM}$ is that we can make a truly single key MAC: the two block cipher calls can use the same block cipher key $K=K_1=K_2$. Moreover, we can derive the hash key as $K_h=\textsf{E}_K(1)$, as long as $|K_h|=n$. Whether we use encryption or decryption in the outer layer makes a huge difference; using the decryption instead enables us to apply an extended version of the mirror theory by Patarin to the security analysis of the construction. $\textsf{DWCDM}$ is secure beyond the birthday bound, roughly up to $2^{2n/3}$ MAC queries and $2^n$ verification queries against nonce-respecting adversaries. $\textsf{DWCDM}$ remains secure up to $2^{n/2}$ MAC queries and $2^n$ verification queries against nonce-misusing adversaries

How to Build Fully Secure Tweakable Blockciphers from Classical Blockciphers

This paper focuses on building a tweakable blockcipher from a classical blockcipher whose input and output wires all have a size of $n$ bits. The main goal is to achieve full $2^n$ security. Such a tweakable blockcipher was proposed by Mennink at FSE\u2715, and it is also the only tweakable blockcipher so far that claimed full $2^n$ security to our best knowledge. However, we find a key-recovery attack on Mennink\u27s proposal (in the proceeding version) with a complexity of about $2^{n/2}$ adversarial queries. The attack well demonstrates that Mennink\u27s proposal has at most $2^{n/2}$ security, and therefore invalidates its security claim. In this paper, we study a construction of tweakable blockciphers denoted as $\tilde{\mathbb E}[s]$ that is built on $s$ invocations of a blockcipher and additional simple XOR operations. As proven in previous work, at least two invocations of blockcipher with linear mixing are necessary to possibly bypass the birthday-bound barrier of $2^{n/2}$ security, we carry out an investigation on the instances of $\tilde{\mathbb E}[s]$ with $s \ge 2$, and find $32$ highly efficient tweakable blockciphers $\widetilde{E1}$, $\widetilde{E2}$, $\ldots$, $\widetilde{E32}$ that achieve $2^n$ provable security. Each of these tweakable blockciphers uses two invocations of a blockcipher, one of which uses a tweak-dependent key generated by XORing the tweak to the key (or to a secret subkey derived from the key). We point out the provable security of these tweakable blockciphers is obtained in the ideal blockcipher model due to the usage of the tweak-dependent key

Improved Security Analysis for Nonce-based Enhanced Hash-then-Mask MACs

In this paper, we prove that the nonce-based enhanced hash-then-mask MAC ($\mathsf{nEHtM}$) is secure up to $2^{\frac{3n}{4}}$ MAC queries and $2^n$ verification queries (ignoring logarithmic factors) as long as the number of faulty queries $\mu$ is below $2^\frac{3n}{8}$, significantly improving the previous bound by Dutta et al. Even when $\mu$ goes beyond $2^{\frac{3n}{8}}$, $\mathsf{nEHtM}$ enjoys graceful degradation of security. The second result is to prove the security of PRF-based $\mathsf{nEHtM}$; when $\mathsf{nEHtM}$ is based on an $n$-to-$s$ bit random function for a fixed size $s$ such that $1\leq s\leq n$, it is proved to be secure up to any number of MAC queries and $2^s$ verification queries, if (1) $s=n$ and $\mu<2^{\frac{n}{2}}$ or (2) $\frac{n}{2}<s<2^{n-s}$ and $\mu<\max\{2^{\frac{s}{2}},2^{n-s}\}$, or (3) $s\leq \frac{n}{2}$ and $\mu<2^{\frac{n}{2}}$. This result leads to the security proof of truncated $\mathsf{nEHtM}$ that returns only $s$ bits of the original tag since a truncated permutation can be seen as a pseudorandom function. In particular, when $s\leq\frac{2n}{3}$, the truncated $\mathsf{nEHtM}$ is secure up to $2^{n-\frac{s}{2}}$ MAC queries and $2^s$ verification queries as long as $\mu<\min\{2^{\frac{n}{2}},2^{n-s}\}$. For example, when $s=\frac{n}{2}$ (resp. $s=\frac{n}{4}$), the truncated $\mathsf{nEHtM}$ is secure up to $2^{\frac{3n}{4}}$ (resp. $2^{\frac{7n}{8}}$) MAC queries. So truncation might provide better provable security than the original $\mathsf{nEHtM}$ with respect to the number of MAC queries